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1
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Ramundo F, Rossi E, Peris K, Pontecorvi A, Sani G, Betti S, Marietta M, De Stefano V. Improving the management of Polycythemia Vera patients eligible for cytoreduction: report of a multidisciplinary advisory board. Curr Med Res Opin 2025; 41:239-245. [PMID: 39882590 DOI: 10.1080/03007995.2025.2458531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Revised: 01/19/2025] [Accepted: 01/20/2025] [Indexed: 01/31/2025]
Abstract
INTRODUCTION The management of patients with Polycythemia Vera (PV) traditionally includes low-dose aspirin, phlebotomy, and cytoreductive therapy for high-risk individuals. Recent evidence suggests that cytoreductive treatment may be warranted for patients with additional risk factors beyond the traditional criteria of a history of thrombosis and age over 60 years. Introducing new therapeutic agents, including ropeginterferon alfa-2b and ruxolitinib, enables a more personalized treatment approach tailored to individual patient characteristics. CASE REPORT This report presents three complex clinical scenarios involving patients with PV who required cytoreductive therapy, which were discussed by a multidisciplinary advisory board. Each case is accompanied by a concise literature review and recommendations from non-hematologist specialists on managing adverse events associated with cytoreductive treatment. A multidisciplinary expert panel has identified three conceptual pathways to guide clinicians in selecting cytoreductive therapies and managing their associated complications. CONCLUSION The advent of new criteria for starting cytoreduction and the approval of novel drugs for PV has increased the complexity of selecting appropriate cytoreductive therapies. A multidisciplinary approach is increasingly essential to ensure personalized care that maximizes tolerability and minimizes adverse events, particularly given the often chronic nature of the treatment.
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Affiliation(s)
- Francesco Ramundo
- Section of Hematology, Department of Radiological and Hematological Sciences, Catholic University, Fondazione Policlinico Gemelli IRCCS, Rome, Italy
| | - Elena Rossi
- Section of Hematology, Department of Radiological and Hematological Sciences, Catholic University, Fondazione Policlinico Gemelli IRCCS, Rome, Italy
| | - Ketty Peris
- Dermatology, Department of Translational Medicine and Surgery, Catholic University, Fondazione Policlinico Gemelli IRCCS, Rome, Italy
| | - Alfredo Pontecorvi
- Section of Endocrinology, Department of Translational Medicine and Surgery, Catholic University, Fondazione Policlinico Gemelli IRCCS, Rome, Italy
| | - Gabriele Sani
- Section of Psychiatry, Department of Neuroscience, Catholic University, Fondazione Policlinico Gemelli IRCCS, Rome, Italy
| | - Silvia Betti
- Section of Hematology, Department of Radiological and Hematological Sciences, Catholic University, Fondazione Policlinico Gemelli IRCCS, Rome, Italy
| | - Marco Marietta
- Hematology Unit, Azienda Ospedaliero-Universitaria, Modena, Italy
| | - Valerio De Stefano
- Section of Hematology, Department of Radiological and Hematological Sciences, Catholic University, Fondazione Policlinico Gemelli IRCCS, Rome, Italy
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2
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Kirito K. Silent Thyroiditis Associated with Ropeginterferon α-2b in a Patient with Polycythemia Vera. Intern Med 2024; 63:843-846. [PMID: 37532547 PMCID: PMC11008998 DOI: 10.2169/internalmedicine.2171-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 06/19/2023] [Indexed: 08/04/2023] Open
Abstract
Interferon is an emerging treatment option for myeloproliferative neoplasms (MPNs), especially for polycythemia vera (PV). Previous studies of interferon used therapeutically for hepatitis C have demonstrated that one of the most important adverse events associated with interferon treatment is thyroid dysfunction, and a management strategy for thyroid dysfunction has been established. However, whether or not the recommendation is also suitable for MPN settings is unclear. In this study, one PV patient developed silent thyroiditis during a phase 2 study of ropeginterferon α-2b. This case suggests that thyroid dysfunction is an important clinical issue to consider in interferon treatment for PV.
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Affiliation(s)
- Keita Kirito
- Department of Hematology and Oncology, University of Yamanashi, Japan
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3
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Liu Y, Zheng Y, Lin X, Cao Z, Lu J, Ma L, Ren S, Zheng S, Hu Z, Xu B, Chen X. Analysis of clinical characteristics of thyroid disorders in patients with chronic hepatitis B treated with pegylated-interferon alpha. BMC Endocr Disord 2023; 23:115. [PMID: 37217910 DOI: 10.1186/s12902-023-01371-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 05/12/2023] [Indexed: 05/24/2023] Open
Abstract
BACKGROUND Thyroid disorders (TD) is a common complication of pegylated-interferon alpha (Peg-IFNα) therapy. Few studies have investigated the relationship between TD and the efficacy of interferon therapy for chronic hepatitis B (CHB). Therefore, we analyzed the clinical characteristics of TD in patients with CHB treated with Peg-IFNα, and evaluated the correlation between TD and Peg-IFNα treatment efficacy. METHODS In this retrospective study, the clinical data of 146 patients with CHB receiving Peg-IFNα therapy were collected and analyzed. RESULTS During the course of Peg-IFNα therapy, positive conversion of thyroid autoantibodies and TD occurred in 7.3% (85/1158) and 8.8% (105/1187) patients, respectively, and was diagnosed more often in women. The most common thyroid disorder was hyperthyroidism (53.3%), followed by subclinical hypothyroidism (34.3%). We found that thyroid function returned to normal in 78.7% of patients with CHB, and thyroid antibody levels returned to the negative range in approximately 50% of patients after interferon treatment cessation. Only 25% of patients with clinical TD required treatment. Compared with patients with hypothyroidism/subclinical hypothyroidism, patients with hyperthyroidism/subclinical hyperthyroidism showed greater reduction and seroclearance of hepatitis B surface antigen (HBsAg) levels. CONCLUSIONS TD are not an absolute contraindication for interferon therapy; however, patients should be monitored closely during interferon therapy. In pursuit of functional cure, a balance between efficacy and safety must be achieved.
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Affiliation(s)
- Yisi Liu
- First Department of Liver Disease Center, Beijing Youan Hospital, Capital Medical University, No.8, Xi Tou Tiao, Youanmen Wai, Beijing, 100069, Fengtai District, China
| | - Yanhong Zheng
- First Department of Liver Disease Center, Beijing Youan Hospital, Capital Medical University, No.8, Xi Tou Tiao, Youanmen Wai, Beijing, 100069, Fengtai District, China
| | - Xiao Lin
- First Department of Liver Disease Center, Beijing Youan Hospital, Capital Medical University, No.8, Xi Tou Tiao, Youanmen Wai, Beijing, 100069, Fengtai District, China
| | - Zhenhuan Cao
- Third Department of Liver Disease Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Junfeng Lu
- First Department of Liver Disease Center, Beijing Youan Hospital, Capital Medical University, No.8, Xi Tou Tiao, Youanmen Wai, Beijing, 100069, Fengtai District, China
| | - Lina Ma
- First Department of Liver Disease Center, Beijing Youan Hospital, Capital Medical University, No.8, Xi Tou Tiao, Youanmen Wai, Beijing, 100069, Fengtai District, China
| | - Shan Ren
- First Department of Liver Disease Center, Beijing Youan Hospital, Capital Medical University, No.8, Xi Tou Tiao, Youanmen Wai, Beijing, 100069, Fengtai District, China
| | - Sujun Zheng
- First Department of Liver Disease Center, Beijing Youan Hospital, Capital Medical University, No.8, Xi Tou Tiao, Youanmen Wai, Beijing, 100069, Fengtai District, China
| | - Zhongjie Hu
- First Department of Liver Disease Center, Beijing Youan Hospital, Capital Medical University, No.8, Xi Tou Tiao, Youanmen Wai, Beijing, 100069, Fengtai District, China
| | - Bin Xu
- Second Department of Liver Disease Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Xinyue Chen
- First Department of Liver Disease Center, Beijing Youan Hospital, Capital Medical University, No.8, Xi Tou Tiao, Youanmen Wai, Beijing, 100069, Fengtai District, China.
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Papadopoulos VE, Skarlis C, Evangelopoulos ME, Mavragani CP. Type I interferon detection in autoimmune diseases: challenges and clinical applications. Expert Rev Clin Immunol 2021; 17:883-903. [PMID: 34096436 DOI: 10.1080/1744666x.2021.1939686] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
INTRODUCTION Accumulating data highlights that the dysregulation of type I interferon (IFN) pathways plays a central role in the pathogenesis of several systemic and organ-specific autoimmune diseases. Advances in understanding the role of type I IFNs in these disorders can lead to targeted drug development as well as establishing potential disease biomarkers. AREAS COVERED Here, we summarize current knowledge regarding the role of type I IFNs in the major systemic, as well as organ-specific, autoimmune disorders, including prominent inflammatory CNS disorders like multiple sclerosis. EXPERT OPINION Type I IFN involvement and its clinical associations in a wide spectrum of autoimmune diseases represents a promising area for research aiming to unveil common pathogenetic pathways in systemic and organ-specific autoimmunity.
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Affiliation(s)
- Vassilis E Papadopoulos
- Demyelinating Diseases Unit, First Department of Neurology, Eginition Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Charalampos Skarlis
- Department of Physiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria-Eleftheria Evangelopoulos
- Demyelinating Diseases Unit, First Department of Neurology, Eginition Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Clio P Mavragani
- Department of Physiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.,Joint Academic Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
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5
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Mo Z, Tang J, Wu Z, Chen D, Xie D, Wang P. Ulcerative colitis triggered by pegylated interferon alpha-2b in a patient with chronic hepatitis B: A case report and literature review. LIVER RESEARCH 2021; 5:97-101. [PMID: 39959345 PMCID: PMC11791849 DOI: 10.1016/j.livres.2021.04.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 03/13/2021] [Accepted: 04/05/2021] [Indexed: 02/16/2023]
Abstract
Interferon (IFN) is a multifaceted immunomodulator that is effective against many diseases, including chronic hepatitis B and chronic hepatitis C infection. IFN defends against viral infection, but may also cause various side effects, such as ulcerative colitis (UC). Herein, we present a case of UC triggered by pegylated interferon alpha-2b (PEG-IFN-α-2b) therapy in a patient with concurrent chronic hepatitis B (CHB) infection. The diagnosis was based on typical clinical symptoms, colonoscopy findings, colonic mucosal biopsy, and histopathology. Accordingly, treatment with mesalazine was initiated without stopping PEG-IFN-α-2b. Fortunately, UC relieved gradually without compromising the effects of treatment. Simultaneously, we conducted a literature review of previously published case reports on the side effect of UC in patients with underlying chronic hepatitis. Various reactions have been reported, including induction, exacerbation, and no change. This is the first report of UC triggered by PEG-IFN-α-2b in a CHB patient. We recommend that physicians pay attention to the rare side effect of UC during administration of PEG-IFN-α-2b. Mesalazine can relieve UC with sustained use of PEG-IFN-α-2b.
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Affiliation(s)
- Zhishuo Mo
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jian Tang
- Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zeqian Wu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Dabiao Chen
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Dongying Xie
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Peipei Wang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Troshina EA, Panfilova EA, Mikhina MS, Kim IV, Senyushkina ES, Glibka AA, Shifman BM, Larina AA, Sheremeta MS, Degtyarev MV, Rumyanstsev PO, Kuznetzov NS, Melnichenko GA, Dedov II. [Clinical practice guidelines for acute and chronic thyroiditis (excluding autoimmune thyroiditis)]. ACTA ACUST UNITED AC 2021; 67:57-83. [PMID: 34004104 PMCID: PMC8926135 DOI: 10.14341/probl12747] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 04/12/2021] [Indexed: 01/25/2023]
Abstract
Острые и хронические заболевания щитовидной железы занимают второе место по выявляемости после сахарного диабета. Всемирная организация здравоохранения отмечает ежегодную тенденцию к увеличению числа заболеваний щитовидной железы. В настоящих клинических рекомендациях будут рассмотрены вопросы этиологии, клинического течения, диагностики и лечения острых и хронических (за исключением аутоиммунного) воспалительных заболеваний щитовидной железы.Клинические рекомендации — это основной рабочий инструмент практикующего врача, как специалиста, так и врача узкой практики. Лаконичность, структурированность сведений об определенной нозологии, методов ее диагностики и лечения, базирующихся на принципах доказательной медицины, позволяют в короткий срок дать тот или иной ответ на интересующий вопрос специалисту, добиваться максимальной эффективности и персонализации лечения.Клинические рекомендации составлены профессиональным сообществом узких специалистов, одобрены экспертным советом Министерства здравоохранения РФ. Представленные рекомендации содержат максимально полную информацию, которая требуется на этапе диагностики острых и хронических тиреоидитов, этапе выбора тактики ведения пациентов с тиреоидитом, а также на этапе лечения пациента.Рабочая группа представляет этот проект в профессиональном журнале, посвященном актуальным проблемам эндокринологии, с целью повышения качества оказываемой медицинской помощи, повышения эффективности лечения острых и хронических тиреоидитов путем ознакомления с полным тестом клинических рекомендаций по острым и хроническим тиреоидитам (исключая аутоиммунный тиреоидит) максимально возможного количества специалистов в области не только эндокринологии, но и медицины общей (семейной) практики.
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Affiliation(s)
| | | | | | - I V Kim
- Endocrinology Research Centre
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Worth C, Briggs TA, Padidela R, Balmer E, Skae M. Endocrinopathies in Aicardi Goutières syndrome-A descriptive case series. Clin Case Rep 2020; 8:2181-2185. [PMID: 33235754 PMCID: PMC7669429 DOI: 10.1002/ccr3.3081] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 04/28/2020] [Accepted: 06/06/2020] [Indexed: 11/29/2022] Open
Abstract
Hypothyroidism and diabetes insipidus present in children with Aicardi Goutières Syndrome (AGS) often years after disease onset and frequently resolve spontaneously. Screening and regular reassessment for both conditions are recommended in all children with AGS.
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Affiliation(s)
- Chris Worth
- Department of Paediatric EndocrinologyRoyal Manchester Children's HospitalManchesterUK
| | - Tracy A Briggs
- Manchester Centre for Genomic MedicineSt Mary's HospitalManchester Academic Health Sciences CentreManchester University Hospitals NHS Foundation TrustManchesterUK
- Division of Evolution and Genomic SciencesSchool of Biological SciencesUniversity of ManchesterManchesterUK
| | - Raja Padidela
- Department of Paediatric EndocrinologyRoyal Manchester Children's HospitalManchesterUK
| | - Eleanor Balmer
- Department of PaediatricsRoyal Manchester Children's HospitalManchesterUK
| | - Mars Skae
- Department of Paediatric EndocrinologyRoyal Manchester Children's HospitalManchesterUK
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Lopalco G, Rigante D, Lopalco A, Emmi G, Venerito V, Vitale A, Capozio G, Denora N, Cantarini L, Iannone F. Safety of systemic treatments for Behçet's syndrome. Expert Opin Drug Saf 2020; 19:1269-1301. [PMID: 32883123 DOI: 10.1080/14740338.2020.1817379] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Treatment of Behçet's syndrome (BS) is aimed at controlling all symptoms of such a complex disorder, ensuring a good quality of life and preventing life-threatening complications. A better understanding of the pathogenic role of different chemokines has improved our knowledge of BS and elicited a more specific use of therapies currently available, minimizing the burden of potential side-effects related to treatment. AREAS COVERED This work aims to provide a detailed overview of the safety profile for current therapies available in the treatment of BS, focusing on the main side-effects, toxicity and contraindications. EXPERT OPINION The greatest experience in the management of BS has been achieved with the employment of monoclonal anti-tumor necrosis factor antibodies which have been advocated for BS refractory manifestations. Moreover, interleukin-1 inhibitors have proven to be effective as well as safe, despite escalation of their dosage, especially to manage the most severe and difficult-to-treat ocular manifestations. However, general treatment of BS patients remains awkward as protean clinical features may respond differently to the same treatment or even worsen. Therefore, patients' safety for therapies used in BS promotes the implementation of precision medicine, which could help targeting accurately the pathogenetic mechanisms concealed behind specific clinical phenotypes.
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Affiliation(s)
- Giuseppe Lopalco
- Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari , Bari, Italy
| | - Donato Rigante
- Department of Life Sciences and Public Health, Fondazione Policlinico Universitario "A. Gemelli" IRCCS , Rome, Italy.,Università Cattolica Sacro Cuore , Rome, Italy
| | - Antonio Lopalco
- Department of Pharmacy - Drug Sciences, University of Bari , Bari, Italy
| | - Giacomo Emmi
- Department of Experimental and Clinical Medicine, University of Florence , Florence, Italy
| | - Vincenzo Venerito
- Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari , Bari, Italy
| | - Antonio Vitale
- Research Centre of Systemic Autoinflammatory Diseases, Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Centre, Department of Medical Sciences, Surgery and Neurosciences, University of Siena , Siena, Italy
| | - Giovanna Capozio
- Department of Life Sciences and Public Health, Fondazione Policlinico Universitario "A. Gemelli" IRCCS , Rome, Italy
| | - Nunzio Denora
- Department of Pharmacy - Drug Sciences, University of Bari , Bari, Italy
| | - Luca Cantarini
- Research Centre of Systemic Autoinflammatory Diseases, Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Centre, Department of Medical Sciences, Surgery and Neurosciences, University of Siena , Siena, Italy
| | - Florenzo Iannone
- Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari , Bari, Italy
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9
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Ho CW, Chen HH, Hsieh MC, Chen CC, Hsu SP, Yip HT, Kao CH. Hashimoto's thyroiditis might increase polycystic ovary syndrome and associated comorbidities risks in Asia. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:684. [PMID: 32617304 PMCID: PMC7327368 DOI: 10.21037/atm-19-4763] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Background To investigate whether increased the comorbidities such as coronary artery disease (CAD) and risks between Hashimoto’s thyroiditis (HT) and polycystic ovary syndrome (PCOS) in Taiwanese women. Methods Patients newly diagnosed as having HT during 2000–2012 were assigned to the case group. Cases and controls were matched for age and comorbidities at a 1:2 ratio using propensity score matching. Incidence was calculated in the unit of 1000 person-year. Univariate and multivariate Cox proportional hazard regression, multivariate Cox, logistic regression, and Kaplan-Meier analyses were performed. Results Among 3,996 participants, 2,664 constituted the control group and 1,332 constituted the case group. The PCOS risk in patients with HT increased by 2.37 times [95% confidence interval (CI): 1.22–4.62] compared with the controls. Hypertension (HTN) [adjusted odds ratio (OR): 1.31, 95% CI: 1.03–1.66] and hyperlipidemia (adjusted OR: 1.55, 95% CI: 1.2–1.9) were more common in HT patients without PCOS than in other patients. The adjusted OR for CAD in patients with HT was 1.51 (95% CI: 1.11–2.06), whereas that in patients with HT and PCOS was 5.92 (95% CI: 1.32–26.53). Conclusions In our study, the PCOS risk in patients with HT increased by 2.37 times, which is lower than the increase in HT risk in Asian patients with PCOS (4.56 times). The proportion of CAD increased significantly by 5.92 times in patients with HT and PCOS compared with patients with HT only.
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Affiliation(s)
- Chun-Wei Ho
- Intelligent Diabetes Metabolism and Exercise Center, China Medical University Hospital, Taichung
| | - Hsin-Hung Chen
- Intelligent Diabetes Metabolism and Exercise Center, China Medical University Hospital, Taichung.,School of Medicine, Institute of Medicine and Public Health, Chung Shan, Medical University, Taichung
| | - Ming-Chia Hsieh
- Intelligent Diabetes Metabolism and Exercise Center, China Medical University Hospital, Taichung.,Graduate Institute of Integrative Medicine, China Medical University, Taichung.,Division of Clinical Nutrition, Department of Internal Medicine, China Medical University Hospital, Taichung
| | - Ching-Chu Chen
- Division of Endocrinology and Metabolism, Department of Internal Medicine, China Medical University Hospital, Taichung.,School of Chinese Medicine, China Medical University, Taichung
| | - Sheng-Pang Hsu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, China Medical University Hospital, Taichung
| | - Hei-Tung Yip
- Management Office for Health Data, China Medical University Hospital, Taichung.,School of Medicine, College of Medicine China Medical University, Taichung
| | - Chia-Hung Kao
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung.,Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung.,Department of Bioinformatics and Medical Engineering, Asia University, Taichung.,Center of Augmented Intelligence in Healthcare, China Medical University Hospital, Taichung
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10
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Rouland A, Buffier P, Petit JM, Vergès B, Bouillet B. [Thyroiditis: What's new in 2019?]. Rev Med Interne 2020; 41:390-395. [PMID: 32107053 DOI: 10.1016/j.revmed.2020.02.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Accepted: 02/01/2020] [Indexed: 11/19/2022]
Abstract
Thyroiditis is a frequent and mostly benign disease that can sometimes disrupt the thyroid balance. Their diagnosis, as well as their aetiology, is a necessary step in the management of the patients. Painful thyroiditis includes acute thyroiditis of infectious origin and subacute thyroiditis. The first one can be treated by antibiotics or antifungals depending on the germ found. The second one will be treated with non-steroidal anti-inflammatory drugs or corticosteroids. In cases of Hashimoto's thyroiditis with overt hypothyroidism, replacement therapy with L-thyroxine will be adapted to the TSH level. As amiodarone treatment provides dysthyroidism, the thyroid status should be monitored regularly. Hypothyroidism will be treated using thyroid replacement therapy. Hyperthyroidism imposes a stop of amiodarone when it is possible. Treatment with synthetic antithyroid drugs (propyl-thio-uracil) or corticosteroids could be used whether there is an underlying thyroid disease or not. Immunotherapies with anti-PD-1/PDL1 or anti-CTLA-4 can also provide dysthyroidism. A monitoring of the thyroid assessment needs to be done in these patients, even if there are no clinical signs, which are not very specific in this context. The treatment of hypothyroidism will be based on thyroid replacement therapy according to the TSH level and the presence or absence of anti-TPO antibodies. Treatment of symptomatic hyperthyroidism may involve a prescription of beta-blockers, or synthetic antithyroid drugs in case of positive anti-TSH receptor antibodies. In all cases, it is desirable to contact an endocrinologist to confirm the diagnosis hypothesis and to decide on a suitable treatment.
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Affiliation(s)
- A Rouland
- Service d'endocrinologie, diabétologie, maladies métaboliques, CHU de Dijon, 2, boulevard Maréchal-de-Lattre-de-Tassigny, 21000 Dijon, France; Unité Inserm LNC-UMR 1231, université de Bourgogne-Franche-Comté, Dijon, France
| | - P Buffier
- Service d'endocrinologie, diabétologie, maladies métaboliques, CHU de Dijon, 2, boulevard Maréchal-de-Lattre-de-Tassigny, 21000 Dijon, France
| | - J-M Petit
- Service d'endocrinologie, diabétologie, maladies métaboliques, CHU de Dijon, 2, boulevard Maréchal-de-Lattre-de-Tassigny, 21000 Dijon, France; Unité Inserm LNC-UMR 1231, université de Bourgogne-Franche-Comté, Dijon, France
| | - B Vergès
- Service d'endocrinologie, diabétologie, maladies métaboliques, CHU de Dijon, 2, boulevard Maréchal-de-Lattre-de-Tassigny, 21000 Dijon, France; Unité Inserm LNC-UMR 1231, université de Bourgogne-Franche-Comté, Dijon, France
| | - B Bouillet
- Service d'endocrinologie, diabétologie, maladies métaboliques, CHU de Dijon, 2, boulevard Maréchal-de-Lattre-de-Tassigny, 21000 Dijon, France; Unité Inserm LNC-UMR 1231, université de Bourgogne-Franche-Comté, Dijon, France.
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Bhattacharya S, Goyal A, Kaur P, Singh R, Kalra S. Anticancer Drug-induced Thyroid Dysfunction. EUROPEAN ENDOCRINOLOGY 2020; 16:32-39. [PMID: 32595767 DOI: 10.17925/ee.2020.16.1.32] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Accepted: 11/08/2019] [Indexed: 12/15/2022]
Abstract
Cancer immunotherapy and targeted therapy, though less toxic than conventional chemotherapy, can increase the risk of thyroid dysfunction. Immune checkpoint inhibitors render the cancer cells susceptible to immune destruction, but also predispose to autoimmune disorders like primary hypothyroidism as well as central hypothyroidism secondary to hypophysitis. Tyrosine kinase inhibitors act by blocking vascular endothelial growth factor receptors and their downstream targets. Disruption of the vascular supply from the inhibition of endothelial proliferation damages not only cancer cells but also organs with high vascularity like the thyroid. Interferon-α, interleukin-2 and thalidomide analogues can cause thyroid dysfunction by immune modulation. Alemtuzumab, a monoclonal antibody directed against the cell surface glycoprotein CD52 causes Graves' disease during immune reconstitution. Metaiodobenzylguanidine, combined with 131-iodine, administered as a radiotherapeutic agent for tumours derived from neural crest cells, can cause primary hypothyroidism. Bexarotene can produce transient central hypothyroidism by altering the feedback effect of thyroid hormone on the pituitary gland. Thyroid dysfunction can be managed in the usual manner without a requirement for dose reduction or discontinuation of the implicated agent. This review aims to highlight the effect of various anticancer agents on thyroid function. Early recognition and appropriate management of thyroid disorders during cancer therapy will help to improve treatment outcomes.
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Affiliation(s)
| | - Alpesh Goyal
- All Indian Institute of Medical Sciences, New Delhi, India
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12
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Hong SJ, Choe BH. Strategies for treating and managing chronic hepatitis C in children in the direct-acting antiviral era. Clin Exp Pediatr 2020; 63:46-47. [PMID: 32024333 PMCID: PMC7029664 DOI: 10.3345/kjp.2019.01116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 11/03/2019] [Indexed: 11/27/2022] Open
Affiliation(s)
- Suk-Jin Hong
- Department of Pediatrics, School of Medicine, Daegu Catholic University, Daegu, Korea
| | - Byung-Ho Choe
- Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea
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13
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Lowenstein A, Fainboim H, Reyes A, Lutzky C, Ameigeiras B, Schroder T, Eugenio Russmann ML. Autoimmune and non-autoimmune thyroid dysfunction in HCV infected and HCV-HIV co-infected patients before and after interferon alpha therapy: A prospective study. ACTA ACUST UNITED AC 2019; 67:263-271. [PMID: 31266712 DOI: 10.1016/j.endinu.2019.04.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Revised: 04/16/2019] [Accepted: 04/26/2019] [Indexed: 11/24/2022]
Abstract
INTRODUCTION Autoimmune thyroid diseases are reported in no treated hepatitis C virus (HCV) infection. The standard interferon alpha (IFNα) treatment is associated with an increase of thyroid damage and dysfunction. The present cohort prospective study compared thyroid function and autoimmunity in HCV patients' monoinfected and coinfected HCV-HIV at baseline, during and after IFNα therapy. METHODS We studied 790 HCV infected patients: G1 (monoinfected HCV: N=580) and G2 (HCV-HIV coinfected: N=210). They were evaluated for thyroid function and thyroid tiroperoxidase antibodies (TPOAb) at baseline and 235 patients (G1: 183; G2: 52) post IFNα therapy. If thyroid dysfunction (TD) was diagnosed, they were reevaluated at 12 month after discontinuation to determine whether the TD was transitory or definitive. RESULTS No difference was found in the prevalence of TD at baseline in G1 (7.6%) and G2 (9%). However, monoinfected patients showed a higher prevalence of TPOAb positivity with a women preponderance in this group. There was no difference in TD between both groups during IFNα therapy (G1 23.5% vs G2 19.2%). In G1 the autoimmune TD was higher than in G2 (67.4% vs 30%, p=0.02). Autoimmune TD during IFNα tended to evolve to definitive hypothyroidism and non-autoimmune TD recovered euthyroidism after IFNα discontinuation. The presence of positive TPOAb (RR 3.55) and female gender (RR 2.4) were associated with the development of TD with IFNα therapy. CONCLUSION Our hypothesis is the importance of HCV in G1 and G2, combined with IFNα in triggering TD and TPOAb positivity, not described in other diseases' applications.
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Affiliation(s)
- Alicia Lowenstein
- Endocrinology Division, Ramos Mejia Hospital, Urquiza 609, Buenos Aires, Argentina.
| | - Hugo Fainboim
- Infectious Liver Diseases Department, Francisco J Muñiz Hospital, Uspallata 2272, Buenos Aires, Argentina
| | - Adriana Reyes
- Endocrinology Division, Ramos Mejia Hospital, Urquiza 609, Buenos Aires, Argentina
| | - Cynthia Lutzky
- Endocrinology Division, Ramos Mejia Hospital, Urquiza 609, Buenos Aires, Argentina
| | - Beatriz Ameigeiras
- Hepatology Department, Ramos Mejia Hospital, Urquiza 609, Buenos Aires, Argentina
| | - Teresa Schroder
- Infectious Liver Diseases Department, Francisco J Muñiz Hospital, Uspallata 2272, Buenos Aires, Argentina
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Kuna L, Jakab J, Smolic R, Wu GY, Smolic M. HCV Extrahepatic Manifestations. J Clin Transl Hepatol 2019; 7:172-182. [PMID: 31293918 PMCID: PMC6609844 DOI: 10.14218/jcth.2018.00049] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2018] [Revised: 02/21/2019] [Accepted: 03/17/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) has been shown to affect many tissues other than liver. However, of the many extrahepatic manifestations (EMs) that have been associated with HCV, including cryoglobulinemia, lymphoma, insulin resistance, type 2 diabetes and neurological disorders, only a few have been shown to be directly related to HCV infection of extrahepatic tissues. HCV-triggered immune-mediated mechanisms account for most of the EMs. It is estimated that up to 74% of patients with chronic hepatitis C can develop at least one EM. All HCV patients with EMs should be considered for antiviral therapy, although not all will resolve with sustained virological response.
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Affiliation(s)
- Lucija Kuna
- Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek, Croatia
| | - Jelena Jakab
- Department of Pathophysiology and Physiology with Immunology, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek, Croatia
- Department of Internal Medicine, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia
| | - Robert Smolic
- Department of Pathophysiology and Physiology with Immunology, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek, Croatia
- Department of Pharmacology, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia
| | - George Y Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
| | - Martina Smolic
- Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek, Croatia
- Department of Pharmacology, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia
- *Correspondence to: Martina Smolic, Department of Pharmacology, J. J. Strossmayer University of Osijek Faculty of Medicine Osijek, J. Huttlera 4, Osijek 31000, Croatia. Tel: + 385-31-512-800, Fax: +385-31-512-833, E-mail:
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Yao Q, An X, Zhang J, Mu K, Li L, Song R, Sun P, Zhang JA. IRF7 Gene Variations Confer Susceptibility to Autoimmune Thyroid Diseases and Graves' Ophthalmopathy. Int J Endocrinol 2019; 2019:7429187. [PMID: 30774658 PMCID: PMC6350596 DOI: 10.1155/2019/7429187] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Accepted: 11/01/2018] [Indexed: 01/20/2023] Open
Abstract
The objective of this study was to investigate whether IRF7 polymorphisms are associated with autoimmune thyroid diseases (AITDs). We selected three single nucleotide polymorphisms (SNPs) of IRF7, namely, rs1061501, rs1131665, and rs1061502 for genotyping using PCR-based ligase detection reaction (LDR) method in a total of 1659 participants (592 with Graves' disease, 297 with Hashimoto's thyroiditis, and 770 healthy controls). Gene-disease and genotype-clinical phenotype associations were evaluated for the three SNPs. Our results showed that the AG genotype and the minor allele G frequency of rs1131665 and rs1061502 in AITD patients were both higher than those of the controls (rs1131665: AG genotype: P = 0.017, OR = 1.968; allele G: P = 0.018, OR = 1.946; rs1061502: AG genotype: P = 0.029, OR = 1.866; allele G: P = 0.031, OR = 1.847). Subgroup analysis also showed that the AG genotype and the minor allele G frequency of rs1131665 and rs1061502 in Graves' disease patients were both higher than those of the controls (rs1131665: AG genotype: P = 0.015, OR = 2.074; allele G: P = 0.016, OR = 2.048; rs1061502: AG genotype: P = 0.034, OR = 1.919; allele G: P = 0.035, OR = 1.898). Furthermore, the allele G frequency of rs1061501 was associated with Graves' ophthalmopathy (P = 0.035, OR = 1.396). No significant difference in IRF7 polymorphisms was found between Hashimoto's thyroiditis patients and controls. Our study has revealed for the first time that IRF7 is a susceptibility gene for AITD, especially for Graves' disease and Graves' ophthalmopathy.
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Affiliation(s)
- Qiuming Yao
- Department of Endocrinology, Jinshan Hospital of Fudan University, No. 1508 Longhang Road, Jinshan District, Shanghai 201508, China
| | - Xiaofei An
- Department of Endocrinology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Jing Zhang
- Department of Endocrinology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, No. 1500 Zhouyuan Road, Pudong District, Shanghai 201318, China
| | - Kaida Mu
- Department of Endocrinology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, No. 1500 Zhouyuan Road, Pudong District, Shanghai 201318, China
| | - Ling Li
- Department of Endocrinology, Jinshan Hospital of Fudan University, No. 1508 Longhang Road, Jinshan District, Shanghai 201508, China
| | - Ronghua Song
- Department of Endocrinology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, No. 1500 Zhouyuan Road, Pudong District, Shanghai 201318, China
| | - Peilong Sun
- Department of General Surgery, Jinshan Hospital of Fudan University, No. 1508 Longhang Road, Jinshan District, Shanghai 201508, China
| | - Jin-an Zhang
- Department of Endocrinology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, No. 1500 Zhouyuan Road, Pudong District, Shanghai 201318, China
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Faustino LC, Lombardi A, Madrigal-Matute J, Owen RP, Libutti SK, Tomer Y. Interferon-α Triggers Autoimmune Thyroid Diseases via Lysosomal-Dependent Degradation of Thyroglobulin. J Clin Endocrinol Metab 2018; 103:3678-3687. [PMID: 30113675 PMCID: PMC6179164 DOI: 10.1210/jc.2018-00541] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Accepted: 07/27/2018] [Indexed: 12/16/2022]
Abstract
CONTEXT Autoimmune thyroid diseases (AITDs) arise from complex interactions among genetic, epigenetic, and environmental factors. Thyroglobulin (TG) is a major susceptibility gene for both Graves disease and Hashimoto thyroiditis. Interferon-α (IFNα), a cytokine secreted during viral infections, has emerged as a key trigger of AITD. We have shown that IFNα upregulates TG transcription; however, how the upregulation of TG transcription by IFNα triggers AITD is still unknown. OBJECTIVE To evaluate how IFNα triggers AITD by testing its effects on TG processing. DESIGN We exposed human thyroid cells to IFNα and evaluated its effects on TG expression and processing. RESULTS Human thyroid cells exposed to INFα had increased levels of TG mRNA but reduced TG protein levels, indicating TG protein degradation. IFNα induced endoplasmic reticulum stress, but surprisingly, neither the use of chemical chaperones nor proteasome inhibitor prevented IFNα-induced TG degradation. IFNα also increased LysoTracker staining and autophagy flux measured by net light chain 3 (LC3)-II and p62 fluxes. In addition, expression of autophagy markers LC3 and autophagy-related gene 5 was higher in thyroid tissues from patients with AITD. Finally, blocking lysosomal degradation prevented IFNα-induced degradation of TG. CONCLUSION We have shown in this study IFNα-induced lysosomal-dependent degradation of TG in human thyroid cells. Our findings suggest that during viral infections, local thyroidal IFNα production can lead to lysosomal TG degradation, releasing pathogenic TG peptides that can trigger AITD.
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Affiliation(s)
- Larissa C Faustino
- Department of Medicine, Albert Einstein College of Medicine, Bronx, New York
- Correspondence and Reprint Requests: Larissa C. Faustino, PhD, Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Forchheimer 702, Bronx, New York 10461. E-mail:
| | - Angela Lombardi
- Department of Medicine, Albert Einstein College of Medicine, Bronx, New York
| | - Julio Madrigal-Matute
- Department of Developmental and Molecular Biology and Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, New York
| | - Randall P Owen
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Steven K Libutti
- Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
| | - Yaron Tomer
- Department of Medicine, Albert Einstein College of Medicine, Bronx, New York
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Lombardi A, Tsomos E, Hammerstad SS, Tomer Y. Interferon alpha: The key trigger of type 1 diabetes. J Autoimmun 2018; 94:7-15. [PMID: 30115527 DOI: 10.1016/j.jaut.2018.08.003] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Revised: 08/04/2018] [Accepted: 08/07/2018] [Indexed: 02/06/2023]
Abstract
IFNα is a cytokine essential to a vast array of immunologic processes. Its induction early in the innate immune response provides a priming mechanism that orchestrates numerous subsequent pathways in innate and adaptive immunity. Despite its beneficial effects in viral infections IFNα has been reported to be associated with several autoimmune diseases including autoimmune thyroid disease, systemic lupus erythematosus, rheumatoid arthritis, primary biliary cholangitis, and recently emerged as a major cytokine that triggers Type 1 Diabetes. In this review, we dissect the role of IFNα in T1D, focusing on the potential pathophysiological mechanisms involved. Evidence from human and mouse studies indicates that IFNα plays a key role in enhancing islet expression of HLA-I in patients with T1D, thereby increasing autoantigen presentation and beta cell activation of autoreactive cytotoxic CD8 T-lymphocytes. The binding of IFNα to its receptor induces the secretion of chemokines, attracting monocytes, T lymphocytes, and NK cells to the infected tissue triggering autoimmunity in susceptible individuals. Furthermore, IFNα impairs insulin production through the induction of endoplasmic reticulum stress as well as by impairing mitochondrial function. Due to its central role in the early phases of beta cell death, targeting IFNα and its pathways in genetically predisposed individuals may represent a potential novel therapeutic strategy in the very early stages of T1D.
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Affiliation(s)
- Angela Lombardi
- Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
| | - Effie Tsomos
- Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Sara S Hammerstad
- Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Aker, Oslo, Norway; Department of Pediatrics, Oslo University Hospital, Ulleval, Oslo, Norway
| | - Yaron Tomer
- Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
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18
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Ghembaza MEA, Lounici A. Safety of Interferon Alpha-2a in Patients with Severe Ophthalmic Behçet’s Disease: Response to Bielefeld et al.’s Letter. Ocul Immunol Inflamm 2018; 26:793-794. [DOI: 10.1080/09273948.2016.1265656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Affiliation(s)
- Mohammed El Amine Ghembaza
- Department of Internal Medicine, Faculty of Medical Sciences, Hospital University Tidjani Damerdji, Tlemcen, Algeria
| | - Ali Lounici
- Department of Internal Medicine, Faculty of Medical Sciences, Hospital University Tidjani Damerdji, Tlemcen, Algeria
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19
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Chalan P, Di Dalmazi G, Pani F, De Remigis A, Corsello A, Caturegli P. Thyroid dysfunctions secondary to cancer immunotherapy. J Endocrinol Invest 2018; 41:625-638. [PMID: 29238906 PMCID: PMC5953760 DOI: 10.1007/s40618-017-0778-8] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Accepted: 10/21/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND Immunotherapy is a firmly established pillar in the treatment of cancer, alongside the traditional approaches of surgery, radiotherapy, and chemotherapy. Like every treatment, also cancer immunotherapy causes a diverse spectrum of side effects, collectively referred to as immune-related adverse events. OBJECTIVE This review will examine the main forms of immunotherapy, the proposed mechanism(s) of action, and the incidence of thyroid dysfunctions. METHODS A comprehensive MEDLINE search was performed for articles published up to March 30, 2017. RESULTS Following the pioneering efforts with administration of cytokines such as IL-2 and IFN-g, which caused a broad spectrum of thyroid dysfunctions (ranging in incidence from 1 to 50%), current cancer immunotherapy strategies comprise immune checkpoint inhibitors, oncolytic viruses, adoptive T-cell transfer, and cancer vaccines. Oncolytic viruses, adoptive T-cell transfer, and cancer vaccines cause thyroid dysfunctions only rarely. In contrast, immune checkpoint blockers (such as anti-CTLA-4, anti-PD-1, anti-PD-L1) are associated with a high risk of thyroid autoimmunity. This risk is highest for anti-PD-1 and increases further when a combination of checkpoint inhibitors is used. CONCLUSIONS Cancer patients treated with monoclonal antibodies that block immune checkpoint inhibitors are at risk of developing thyroid dysfunctions. Their thyroid status should be assessed at baseline and periodically after initiation of the immunotherapy.
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Affiliation(s)
- P Chalan
- Division of Immunology, Department of Pathology, The Johns Hopkins School of Medicine, Ross Building-Room 656, 720 Rutland Avenue, Baltimore, MD, 21205, USA
| | - G Di Dalmazi
- Division of Immunology, Department of Pathology, The Johns Hopkins School of Medicine, Ross Building-Room 656, 720 Rutland Avenue, Baltimore, MD, 21205, USA
- Division of Endocrinology, Department of Medicine and Aging Sciences, "G. D'Annunzio" University of Chieti-Pescara, Chieti, Italy
| | - F Pani
- Division of Immunology, Department of Pathology, The Johns Hopkins School of Medicine, Ross Building-Room 656, 720 Rutland Avenue, Baltimore, MD, 21205, USA
- Endocrinology Unit, Department of Medical Sciences and Public Health Endocrinology, University of Cagliari, Cagliari, Italy
| | - A De Remigis
- Division of Immunology, Department of Pathology, The Johns Hopkins School of Medicine, Ross Building-Room 656, 720 Rutland Avenue, Baltimore, MD, 21205, USA
- Department of Medicine, Arco Hospital, Trento, Italy
| | - A Corsello
- Division of Immunology, Department of Pathology, The Johns Hopkins School of Medicine, Ross Building-Room 656, 720 Rutland Avenue, Baltimore, MD, 21205, USA
- Endocrine Tumor Unit, Department of General Medicine, San Raffaele Scientific Institute, Milan, Italy
| | - P Caturegli
- Division of Immunology, Department of Pathology, The Johns Hopkins School of Medicine, Ross Building-Room 656, 720 Rutland Avenue, Baltimore, MD, 21205, USA.
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Recombinant interferon alpha 2b in rheumatoid arthritis: good antigen for rheumatoid arthritis antibodies. Cent Eur J Immunol 2018; 43:58-68. [PMID: 29736147 PMCID: PMC5927174 DOI: 10.5114/ceji.2018.74874] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2017] [Accepted: 04/18/2017] [Indexed: 02/08/2023] Open
Abstract
Aim of the study Interferon alpha-induced arthritis and activation of the type 1 interferon pathway during rheumatoid arthritis (RA) has been well documented but the underlying mechanism remains unclear. This study addressed the binding specificity of antibodies with recombinant interferon alpha 2b (rIFN α-2b) in sera from different RA patients. Utilization of anti-hrIFN α-2b antibodies as a probe for estimation of interferon α-2b concentration in RA patients’ synovial fluid (SF) was also investigated. Material and methods Binding specificities of antibodies from the sera of 60 RA patients and 35 controls subjects were studied by direct binding, inhibition ELISA, and quantitative precipitation titration. Inhibition ELISA was also used to estimate patients’ SF interferon α-2b concentrations. Results RA IgG from patients’ sera showed strong recognition to hrIFN α-2b in comparison to commercially available interferon (IFN α-2b) (p < 0.05) or the gene encoding this interferon (IFN α-2b gene) (p < 0.05). The affinity of RA antibodies for rIFN α-2b (1.10 × 10–7 M) was found to be high as assessed by Langmuir plot. No significant difference in the level of interferon α in the SF of RA patients was observed as compared to the healthy controls. Conclusions rIFN α-2b presents unique epitopes that might explain the possible antigenic role in the induction of RA antibodies and anti-rIFN α-2b antibodies represent an alternative immunological probe for the estimation of interferon α in the SF of RA patients.
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Bliddal S, Nielsen CH, Feldt-Rasmussen U. Recent advances in understanding autoimmune thyroid disease: the tallest tree in the forest of polyautoimmunity. F1000Res 2017; 6:1776. [PMID: 29043075 PMCID: PMC5621109 DOI: 10.12688/f1000research.11535.1] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/29/2017] [Indexed: 12/17/2022] Open
Abstract
Autoimmune thyroid disease (AITD) is often observed together with other autoimmune diseases. The coexistence of two or more autoimmune diseases in the same patient is referred to as polyautoimmunity, and AITD is the autoimmune disease most frequently involved. The occurrence of polyautoimmunity has led to the hypothesis that the affected patients suffer from a generalized dysregulation of their immune system. The present review summarizes recent discoveries unravelling the immunological mechanisms involved in autoimmunity, ranging from natural autoimmunity to disease-specific autoimmunity. Furthermore, the clinical grounds for considering AITD in a setting of polyautoimmunity are explored. A better understanding of these may pave the way for designing new treatment modalities targeting the underlying immune dysregulation when AITD appears in the context of polyautoimmunity.
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Affiliation(s)
- Sofie Bliddal
- Department of Medical Endocrinology, Section 2132, Copenhagen University Hospital (Rigshospitalet), Blegdamsvej 9, 2100 Copenhagen, Denmark
| | - Claus Henrik Nielsen
- Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, section 7521, Copenhagen University Hospital (Rigshospitalet), Blegdamsvej 9, 2100 Copenhagen, Denmark
| | - Ulla Feldt-Rasmussen
- Department of Medical Endocrinology, Section 2132, Copenhagen University Hospital (Rigshospitalet), Blegdamsvej 9, 2100 Copenhagen, Denmark
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22
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Struja T, Kutz A, Fischli S, Meier C, Mueller B, Recher M, Schuetz P. Is Graves' disease a primary immunodeficiency? New immunological perspectives on an endocrine disease. BMC Med 2017; 15:174. [PMID: 28942732 PMCID: PMC5611589 DOI: 10.1186/s12916-017-0939-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Accepted: 09/04/2017] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Uncertainty about factors influencing the susceptibility and triggers for Graves' disease persists, along with a wide variation in the response to anti-thyroid drugs, currently at approximately 50% of non-responders. The aim of this narrative review is to summarize immunological concepts, with a combined endocrine and immunological perspective, to highlight potential new areas of research. MAIN TEXT Relevant studies were identified through a systematic literature search using the PubMed and EMBASE databases in March 2016. No cut-offs regarding dates were imposed. We used the terms "Graves' Disease" or "Basedow" or "thyrotoxicosis" together with the terms "etiology", "pathophysiology", "immunodeficiency", "causality", and "autoimmunity". The terms "orbitopathy", "ophthalmopathy", and "amiodarone" were excluded. Articles in English, French, German, Croatian, Spanish, and Italian were eligible for inclusion. CONCLUSIONS While concepts such as the impact of iodine, smoking, human leucocyte antigen, infections, and ethnicity are established, new ideas have emerged. Pertaining evidence suggests the involvement of autoimmunity and immunodeficiency in the pathophysiology of Graves' disease. Recent studies point to specific immunological mechanisms triggering the onset of disease, which may also serve as targets for more specific therapies.
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Affiliation(s)
- Tristan Struja
- Medical University Department, Clinic for Endocrinology, Diabetes & Metabolism, Kantonsspital Aarau, Aarau, Switzerland.
| | - Alexander Kutz
- Medical University Department, Clinic for Endocrinology, Diabetes & Metabolism, Kantonsspital Aarau, Aarau, Switzerland
| | - Stefan Fischli
- Medical Clinic, Department for Endocrinology, Diabetes & Metabolism, Kantonsspital Luzern, Luzern, Switzerland
| | - Christian Meier
- Medical Faculty of the University of Basel, Basel, Switzerland.,Division of Endocrinology, Diabetes & Metabolism, University Hospital and University Basel, Basel, Switzerland
| | - Beat Mueller
- Medical University Department, Clinic for Endocrinology, Diabetes & Metabolism, Kantonsspital Aarau, Aarau, Switzerland.,Medical Faculty of the University of Basel, Basel, Switzerland
| | - Mike Recher
- Medical Faculty of the University of Basel, Basel, Switzerland.,Medical Outpatient Clinic and Immunodeficiency Laboratory, Department of Biomedicine, University Hospital and University Basel, Basel, Switzerland
| | - Philipp Schuetz
- Medical University Department, Clinic for Endocrinology, Diabetes & Metabolism, Kantonsspital Aarau, Aarau, Switzerland.,Medical Faculty of the University of Basel, Basel, Switzerland
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Sayiner ZA, Eraydın A, Metin T, Özkaya M. Interferon alpha-induced non-immune thyrotoxicosis treated by plasmapheresis. BMJ Case Rep 2017; 2017:bcr-2017-221228. [PMID: 28951513 DOI: 10.1136/bcr-2017-221228] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Interferon-alpha (IFN-α) is an effective drug used for the treatment of chronic hepatitis C. So far its numerous side effects have been reported in the literature. It may be difficult to always put IFN-induced thyroid diseases into a single classic thyroid disease table. There are numerous atypical thyroid diseases due to IFN usage for hepatitis C virus. Herein, we present a case with a rare clinical table such as thyrotoxicosis observed following IFN-α therapy in a patient with euthyroid nodular thyroid without autoimmune thyroiditis findings and the use of therapeutic apheresis method for the treatment of disease.
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Affiliation(s)
| | - Ayten Eraydın
- Department of Endocrinology and Metabolism, Gaziantep University School of Medicine, Gaziantep, Turkey
| | - Taylan Metin
- Department of Endocrinology and Metabolism, Gaziantep University School of Medicine, Gaziantep, Turkey
| | - Mesut Özkaya
- Department of Endocrinology and Metabolism, Gaziantep University, Gaziantep, Turkey
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French JD, Bible K, Spitzweg C, Haugen BR, Ryder M. Leveraging the immune system to treat advanced thyroid cancers. Lancet Diabetes Endocrinol 2017; 5:469-481. [PMID: 27773653 DOI: 10.1016/s2213-8587(16)30277-7] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Revised: 09/02/2016] [Accepted: 09/05/2016] [Indexed: 12/20/2022]
Abstract
Inflammation has long been associated with the thyroid and with thyroid cancers, raising seminal questions about the role of the immune system in the pathogenesis of advanced thyroid cancers. With a growing understanding of dynamic tumour-immune cell interactions and the mechanisms by which tumour cells evade antitumour immunity, the field of cancer immunotherapy has been revolutionised. In this Review, we provide evidence to support the presence of an antitumour immune response in advanced thyroid cancers linked to cytotoxic T cells and NK cells. This antitumour response, however, is likely blunted by the presence of immunosuppressive pathways within the microenvironment, facilitated by tumour-associated macrophages or increased expression of negative regulators of cytotoxic T-cell function. Current and future efforts to incorporate immune-based therapies into existing tumour cell or endothelial-derived therapies-eg, with kinase inhibitors targeting tumour-associated macrophages or antibodies blocking negative regulators on T cells-could provide improved and durable responses for patients with disease that is otherwise refractory to treatment.
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Affiliation(s)
- Jena D French
- Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Denver, Aurora, CO, USA; University of Colorado Cancer Center, University of Colorado Denver, Aurora, CO, USA
| | - Keith Bible
- Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA
| | - Christine Spitzweg
- Department of Internal Medicine II, University Hospital of Munich, Ludwig-Maximilians-University, Munich, Germany
| | - Bryan R Haugen
- Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Denver, Aurora, CO, USA; Department of Pathology, University of Colorado Denver, Aurora, CO, USA; University of Colorado Cancer Center, University of Colorado Denver, Aurora, CO, USA
| | - Mabel Ryder
- Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA; Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA.
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25
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Retraction notice. Muscle Nerve 2017; 55:766. [DOI: 10.1002/mus.21394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Shpakov AO, Zharova OA, Derkach KV. Antibodies to extracellular regions of G protein-coupled receptors and receptor tyrosine kinases as one of the causes of autoimmune diseases. J EVOL BIOCHEM PHYS+ 2017. [DOI: 10.1134/s1234567817020021] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Kundra A, Wang JC. Interferon induced thrombotic microangiopathy (TMA): Analysis and concise review. Crit Rev Oncol Hematol 2017; 112:103-112. [PMID: 28325251 DOI: 10.1016/j.critrevonc.2017.02.011] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Revised: 12/31/2016] [Accepted: 02/14/2017] [Indexed: 12/17/2022] Open
Abstract
Interferon (IFN) has been associated with development of thrombotic microangiopathy including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). We reviewed literature from the earliest reported association in 1993, to July 2016 and found 68 cases. Analysis of this data shows: (1) Mean age at diagnosis was 47 years (95% CI, 44-50). (2) Majority of cases were seen where IFN was used for the treatment of chronic myelogenous leukemia (CML), multiple sclerosis (MS), chronic hepatitis C virus infection (HCV) and one case each for hairy cell leukemia (HCL) and Sezary syndrome. (3) There were no cases reported for polycythemia vera (PV) or lymphoma. (4) Sex distribution was nearly equivalent with the exception in patients with multiple sclerosis where there was female predominance (12 of 16 with reported data). (5) For pooled analysis, the average duration of treatment with IFN before TMA was diagnosed was 40.4 months. (6) Comparative analysis showed that patients with MS required the highest cumulative dose exposure before developing TMA (MS 68.6 months, CML 35.5 months, HCV 30.4 months). (7) Cases of confirmed TTP (where A disintegrin and Metalloprotease with thrombospondin type 1 motif 13: ADAMTS 13 level was measured) showed presence of an inhibitor. (8) In all cases of confirmed TTP, moderate to severe thrombocytopenia was a striking clinical feature at presentation while this was not a consistent finding in all other cases of TMA. (9) Outcome analysis revealed complete remission in 27 (40%), persistent chronic kidney disease (CKD) in 28 (42%) and fatality in 12 patients (18%). (10) Treatment with corticosteroids, plasma exchange and rituximab resulted in durable responses.
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Affiliation(s)
- Ajay Kundra
- Division of Hematology/Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY, USA
| | - Jen Chin Wang
- Division of Hematology/Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY, USA.
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Bliddal S, Borresen SW, Feldt-Rasmussen U. Thyroid Autoimmunity and Function after Treatment with Biological Antirheumatic Agents in Rheumatoid Arthritis. Front Endocrinol (Lausanne) 2017; 8:179. [PMID: 28824542 PMCID: PMC5534470 DOI: 10.3389/fendo.2017.00179] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Accepted: 07/07/2017] [Indexed: 12/29/2022] Open
Abstract
With the increased pro-inflammatory response in both rheumatoid arthritis and thyroid autoimmune diseases, treatment with biological antirheumatic agents (BAAs) of the former may affect the course of the latter. In hepatitis C and cancer patients, treatment with biological agents substantially increases the risk of developing thyroid autoimmunity. As the use of BAAs in the treatment of rheumatoid arthritis is increasing, this review aimed to investigate if such use affected thyroid status in rheumatoid arthritis patients. We conducted a systematic literature search and included six studies with a total of 311 patients as well as three case reports. The patients were treated with tumor necrosis factor-α inhibitors (infliximab, etanercept, or adalimumab) or the monoclonal CD20-antibody rituximab. There was a non-significant trend of slight improvement of both thyroid function and autoantibody status: a reduction of thyroid peroxidase and thyroglobulin antibody concentrations, and a reduction of thyrotropin levels in hypothyroid patients. Despite the small number of studies, they presented compliant data. The BAAs used in rheumatoid arthritis thus did not seem to negatively affect thyroid status in patients with rheumatoid arthritis and can be considered safe with regard to thyroid autoimmunity. However, the well-established association between rheumatic diseases and thyroid autoimmunity necessitates continued monitoring of thyroid function in patients with rheumatoid arthritis. Each new BAA should be scrutinized for its effect on thyroid as well as other autoimmune diseases in order to establish concise recommendations for patient follow-up for each agent and each disease.
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Affiliation(s)
- Sofie Bliddal
- Department of Medical Endocrinology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Stina Willemoes Borresen
- Department of Medical Endocrinology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Ulla Feldt-Rasmussen
- Department of Medical Endocrinology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- *Correspondence: Ulla Feldt-Rasmussen,
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Khan WA. Recombinant Interferon Alpha-2b is a High-Affinity Antigen for Type 1 Diabetes Autoantibodies. Can J Diabetes 2016; 41:217-223. [PMID: 28024793 DOI: 10.1016/j.jcjd.2016.10.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2016] [Revised: 06/12/2016] [Accepted: 10/03/2016] [Indexed: 11/16/2022]
Abstract
OBJECTIVES Type 1 diabetes results from T-cell-mediated destruction of the beta cells of the pancreas and is associated with several autoimmune phenomena. Many studies have suggested the involvement of interferon alpha (IFN α) in the development of type 1 diabetes, but the exact mechanism remains unclear. In this study, the binding of type 1 diabetes antibodies with recombinant interferon alpha-2b (hrIFN α-2b), their gene (cIFN α-2b gene) and commercially available interferon α-2b (IFN α-2b) were assessed. Furthermore, we also sought to use anti-hrIFN α-2b antibodies as a probe for the estimation of plasma IFN α in patients with type 1 diabetes. METHODS The binding specificity of antibodies was analyzed by direct binding, inhibition ELISA and quantitative precipitin titration in 45 patients with type 1 diabetes and 30 control subjects. Competition ELISA was also used to estimate INF α in the serum of patients with type 1 diabetes. RESULTS Antibodies from type 1 diabetes sera, purified in a protein A-agarose matrix, exhibited greater recognition of hrIFN α-2b than IFN α-2b (p<0.05) and cIFN α-2b gene (p<0.001). The relative affinity of type 1 diabetes antibodies for the hrIFN α-2b, IFN α-2b and cIFN α-2b genes was found to be 1.34×10-7, 1.28×10-6 and 1.13×10-6, respectively. The concentration of plasma INF α evaluated by induced antibodies was found to be significantly higher than in controls (p<0.05). CONCLUSIONS High binding of hrIFN α-2b with IgG from patients with type 1 diabetes might suggest involvement of hrIFN α-2b in type 1 diabetes, especially as an antigenic agent. Anti-hrIFN α-2b antibodies were shown to be good probes for estimation of plasma INF α in patients with type 1 diabetes.
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Affiliation(s)
- Wahid Ali Khan
- Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia.
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Goyal G, Panag K, Garg R. Prevalence of thyroid disorders in hepatitis C virus positive patients on interferon and antiviral therapy. Int J Appl Basic Med Res 2016; 6:245-248. [PMID: 27857890 PMCID: PMC5108099 DOI: 10.4103/2229-516x.192587] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Background: Hepatitis C virus (HCV) infection is common worldwide. The treatment typically involves a combination of interferon-alpha (IFN-α) and ribavirin (RBV) therapy; however, the use of IFN-α is well documented to be associated with thyroid disease, the most common autoimmune disorder associated with IFN-α. Aim: The aim of the present study was to know the prevalence of thyroid abnormality in the HCV-positive patients on IFN and antiviral therapy. Materials and Methods: Fifty known HCV positive patients were enrolled for the study. All the patients were on IFN (3 million unit subcutaneously 3 times/week) and antiviral therapy (oral RBV 1000–1200 mg/day). Thyroid function tests were performed first at the start of treatment and then after 12 weeks of treatment. Results: 13 (26%) of the patients were found to develop hypothyroidism, and 1 (2%) patient developed hyperthyroidism in the course of 12 weeks therapy. Conclusion: HCV patients on IFN and antiviral therapy have an effect on the thyroid gland, so these patients should be regularly screened for thyroid disorders and appropriately treated to maintain euthyroid status.
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Affiliation(s)
- Gitanjali Goyal
- Department of Biochemistry, GGS Medical College, Faridkot, Punjab, India
| | - Kmds Panag
- Department of Biochemistry, GGS Medical College, Faridkot, Punjab, India
| | - Ravinder Garg
- Department of Biochemistry, GGS Medical College, Faridkot, Punjab, India
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El-Folly RF, Maher M. MM, R. Abdelkader A. Thyroid dysfunction in chronic viral hepatitis [B and C]; An Egyptian pilot study. EGYPTIAN LIVER JOURNAL 2016. [DOI: 10.1097/01.elx.0000520136.24876.3e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Hamza I, Eid Y, El-Sayed M, Marzaban R, Abdul-Kareem S. Thyroid Dysfunction in Chronic Hepatitis C Patients Treated with the Combined Pegylated Interferon-Ribavirin Therapy. J Interferon Cytokine Res 2016; 36:527-33. [PMID: 27333271 DOI: 10.1089/jir.2016.0007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Hepatitis C virus (HCV) is an Egyptian serious national health problem. The combination of pegylated interferon (PEG-IFN) with ribavirin (RIB) was considered the established therapy for chronic hepatitis C (CHC), and it was associated with several adverse effects, including thyroid dysfunction (TD). The aim of this work was to study TD in CHC patients receiving PEG-IFN+ RIB therapy. This retrospective study included 100 adult patients attending the outpatient clinics at AL-Kahera Al-Fatemya hospital and were eligible candidates for PEG-IFN+ RIB therapy. Thyroid hormonal profile (thyroid-stimulating hormone, free triiodothyronine, and free thyroxine) was done before initiation of treatment (week 0) and at weeks 12, 24, 48, and 72. The incidence of TD was more evident by the end of treatment (week 48); it was found to be 35%, mostly in the form of hypothyroidism, while the least incidence was detected by week 12 (2%), all in the form of hyperthyroidism. Generally, hypothyroidism was higher than hyperthyroidism in multiple folds. Thyroid profile was not significantly related to viral load.
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Affiliation(s)
- Iman Hamza
- 1 Infectious Diseases and Endemic Hepatogastroenterology, Faculty of Medicine, Cairo University , Cairo, Egypt
| | - Yara Eid
- 2 Endocrinology and Internal Medicine, Faculty of Medicine, Ain Shams University , Cairo, Egypt
| | - Mohammad El-Sayed
- 1 Infectious Diseases and Endemic Hepatogastroenterology, Faculty of Medicine, Cairo University , Cairo, Egypt
| | - Raghda Marzaban
- 1 Infectious Diseases and Endemic Hepatogastroenterology, Faculty of Medicine, Cairo University , Cairo, Egypt
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Khan WA, Qureshi JA. Increased binding of circulating systemic lupus erythematosus autoantibodies to recombinant interferon alpha 2b. APMIS 2015; 123:1016-24. [DOI: 10.1111/apm.12464] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2015] [Accepted: 09/22/2015] [Indexed: 12/09/2022]
Affiliation(s)
- Wahid Ali Khan
- Department of Clinical Biochemistry; College of Medicine; King Khalid University; Abha Saudi Arabia
| | - Javed Anwer Qureshi
- Department of Clinical Biochemistry; College of Medicine; King Khalid University; Abha Saudi Arabia
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Zhang RW, Shao CP, Huo N, Li MR, Xi HL, Yu M, Xu XY. Thyroid dysfunction in Chinese hepatitis C patients: Prevalence and correlation with TPOAb and CXCL10. World J Gastroenterol 2015; 21:9765-9773. [PMID: 26361424 PMCID: PMC4562961 DOI: 10.3748/wjg.v21.i33.9765] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2015] [Revised: 06/02/2015] [Accepted: 07/08/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the relationship among pretreatment serum CXC chemokine ligand 10 (CXCL10), thyroid peroxidase antibody (TPOAb) levels and thyroid dysfunction (TD) in Chinese hepatitis C patients.
METHODS: One hundred and thirty-nine treatment-naive genotype 1 chronic hepatitis C patients with no history of TD or treatment with thyroid hormones were enrolled in this study. Patients underwent peginterferon alfa-2a/ribavirin (PegIFNα-2a/RBV) treatment for 48 wk, followed by detection of clinical factors at each follow-up point. Hepatitis C virus (HCV) antibodies were analyzed using microsomal chemiluminescence, and serum HCV RNA was measured by real-time PCR assay at 0, 4, 12, 24 and 48 wk after the initiation of therapy and 24 wk after the end of therapy. To assess thyroid function, serum thyroid stimulating hormone (TSH), free thyroxine (FT4), free triodothyronine (FT3) and TPOAb/thyroglobulin antibody (TGAb) levels were determined using chemiluminescent immunoassays every 3 mo. Serum CXCL10 levels were determined at baseline.
RESULTS: The prevalence of TD was 18.0%. Twenty-one (84.0%) out of twenty-five patients exhibited normal thyroid function at week 24 after therapy. The rate of sustained virological response to PegIFNα-2a/RBV in our study was 59.0% (82/139), independent of thyroid function. Pretreatment serum CXCL10 levels were significantly increased in patients with euthyroid status compared with patients with TD (495.2 ± 244.2 pg/mL vs 310.0 ± 163.4 pg/mL, P = 0.012). Patients with TD were more frequently TPOAb-positive than non-TD (NTD) patients (24.2% vs 12.3%, P = 0.047) at baseline. Three of the one hundred and fifteen patients without TPOAb at baseline developed TD at the end of treatment (37.5% vs 2.6%, P = 0.000). Female patients exhibited an increased risk for developing TD compared with male patients (P = 0.014).
CONCLUSION: Lower pretreatment serum CXCL10 levels are associated with TD, and TD prevalence increases in female patients and patients who are positive for TPOAb at baseline.
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36
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Feldt-Rasmussen U. Increased risk of thyroid autoimmunity in rheumatoid arthritis. Endocrine 2015; 50:4-5. [PMID: 26100789 DOI: 10.1007/s12020-015-0671-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2015] [Accepted: 06/17/2015] [Indexed: 11/29/2022]
Affiliation(s)
- Ulla Feldt-Rasmussen
- Department of Medical Endocrinology, Rigshospital, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark,
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37
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Kaklamanos M, Thomas D, Pikazis D, Kaltsas G. Thyroid-specific changes following treatment with biological therapies in patients with rheumatic diseases. Endocrine 2015; 50:146-53. [PMID: 25690756 DOI: 10.1007/s12020-015-0551-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2014] [Accepted: 02/07/2015] [Indexed: 12/18/2022]
Abstract
Biological anti-rheumatic agents (BAA) may induce autoimmune phenomena. Evidence on thyroid-specific effects of these agents is relatively limited. We studied prospectively, over 3 years, 36 rheumatic patients treated with BAA (18 Infliximab and 18 Rituximab) and no prior exposure to biological therapies (group-1), with respect to their thyroid function, thyroid antibody titers, and thyroid ultrasonographic parameters, such as left inferior thyroid artery peak systolic velocity (ITA PSV), left thyroid lobe vascularity index (TL VI), and echogenicity. Twenty-eight rheumatic patients treated with disease-modifying anti-rheumatic drugs and/or glucocorticoids (group-2), 21 rheumatic patients not receiving any treatment (group-3), and 49 healthy individuals (group-4) were used for comparison. Thyroid function and autoantibody titers were not significantly altered at any stage irrespectively of the administered BAA, previously unknown autoimmune thyroid disease (AITD) status, and/or concomitant treatment with glucocorticoids. Left ITA PSV was significantly increased in group-1 patients (mean ± SD start: 25.5 ± 14.1 cm/s vs. end: 29.8 ± 11.1 cm/s, p = 0.038 and p < 0.001, respectively). Six group-1, 7 group-2, and 3 group-3 patients developed reduced thyroid echogenicity during follow-up (start: p = 0.003 and end: p < 0.001). Left ITA PSV, left TL VI, and echogenicity changes were not related to alterations in thyroid volume, thyrotropin hormone levels, and/or underlying AITD. Infliximab and Rituximab do not cause any alterations in thyroid function and/or autoimmunity, even in patients with previously undiagnosed AITD. Elevated left ITA PSV and reduced thyroid echogenicity may be early features signaling progression to AITD in patients treated with BAA.
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Affiliation(s)
- Michail Kaklamanos
- Endocrine Unit, Department of Pathophysiology, National and Kapodistrian University of Athens, 75 Mikras Asias St, 11527, Athens, Greece,
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Lin JD, Wang YH, Liu CH, Lin YC, Lin JA, Lin YF, Tang KT, Cheng CW. Association of IRF8 gene polymorphisms with autoimmune thyroid disease. Eur J Clin Invest 2015; 45:711-9. [PMID: 25989711 DOI: 10.1111/eci.12463] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2015] [Accepted: 05/16/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND The occurrence of autoimmune thyroid disease (AITD) is known to have a major adverse effect on interferon (INF)-α treatment. The genetic variant of the INF regulatory factor 8 (IRF8), a type 1 INF regulator, is associated with susceptibility to systemic lupus erythematosus and multiple sclerosis. In this study, we investigated possible associations of the IRF8 polymorphisms, rs17445836 and rs2280381, with AITD in an ethnic Chinese population. MATERIAL AND METHODS In total, 278 patients with Graves' disease (GD) and 55 patients with Hashimoto's thyroiditis (HT), and 252 healthy controls were enrolled. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing were used for genotyping. RESULTS Significantly lower frequencies of the GA genotype and A allele of rs17445836 were found in the HT group than in the control group (P = 0·028, odds ratio (OR) = 4·71 and P = 0·022, OR = 4·40, respectively). Both rs17445836 and rs2280381 were associated with the presence of an antimicrosomal antibody (AmiA), and rs2280381 was also associated with the presence of an antithyroglobulin antibody (ATA) in AITD. Moreover, rs17445836 was associated with the level of AmiA in AITD. CONCLUSIONS rs17445836 of IRF8 is a possible genetic variant associated with the development of HT. rs17445836 was associated with the production of thyroid antibody, and the GG genotype of rs17445836 was associated with a higher AmiA titre than the GA genotype.
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Affiliation(s)
- Jiunn-Diann Lin
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Division of Endocrinology, Department of Internal Medicine, Shuang-Ho Hospital, School of Medicine, College of Medicine, Taipei Medical University, New Taipei City, Taiwan
| | - Yuan-Hung Wang
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Department of Urology, Shuang-Ho Hospital, School of Medicine, College of Medicine, Taipei Medical University, New Taipei City, Taiwan
| | - Chia-Hung Liu
- Department of Family Medicine, Shuang-Ho Hospital, School of Medicine, College of Medicine, Taipei Medical University, New Taipei City, Taiwan
| | - Ying-Chin Lin
- Department of Family Medicine, Shuang-Ho Hospital, School of Medicine, College of Medicine, Taipei Medical University, New Taipei City, Taiwan
| | - Jui-An Lin
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yuh-Feng Lin
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Division of Nephrology, Department of Internal Medicine, Shuang-Ho Hospital, School of Medicine, College of Medicine, Taipei Medical University, New Taipei City, Taiwan
| | - Kam-Tsun Tang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan
| | - Chao-Wen Cheng
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
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Narciso-Schiavon JL, Schiavon LDL. Autoantibodies in chronic hepatitis C: A clinical perspective. World J Hepatol 2015; 7:1074-1085. [PMID: 26052396 PMCID: PMC4450184 DOI: 10.4254/wjh.v7.i8.1074] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Revised: 01/16/2015] [Accepted: 02/09/2015] [Indexed: 02/06/2023] Open
Abstract
Non-organ-specific autoantibodies and thyroid autoantibodies have been frequently found in chronic carriers of hepatitis C virus (HCV). With respect to endomysial antibodies and tissue transglutaminase, it is controversial whether the prevalence of gluten-related seromarkers is higher in patients with HCV. In such cases, in addition to acknowledging any currently existing autoimmune disease, recognizing the risk of the patient developing an autoimmune disease during interferon (IFN)-based treatment must be a principle concern. From a clinical point-of-view, the presence of autoantibodies arouses suspicion that an autoimmune disease may be present or may be precipitated by IFN-based HCV treatment. In this paper, we review the prevalence of autoantibodies in individuals with hepatitis C, the clinical significance of these autoantibodies, and the approach recommended for such situations.
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Genetic-epigenetic dysregulation of thymic TSH receptor gene expression triggers thyroid autoimmunity. Proc Natl Acad Sci U S A 2014; 111:12562-7. [PMID: 25122677 DOI: 10.1073/pnas.1408821111] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Graves disease (GD) is an autoimmune condition caused by interacting genetic and environmental factors. Genetic studies have mapped several single-nucleotide polymorphisms (SNPs) that are strongly associated with GD, but the mechanisms by which they trigger disease are unknown. We hypothesized that epigenetic modifications induced by microenvironmental influences of cytokines can reveal the functionality of GD-associated SNPs. We analyzed genome-wide histone H3 lysine 4 methylation and gene expression in thyroid cells induced by IFNα, a key cytokine secreted during viral infections, and overlapped them with known GD-associated SNPs. We mapped an open chromatin region overlapping two adjacent GD-associated SNPs (rs12101255 and rs12101261) in intron 1 of the thyroid stimulating hormone receptor (TSHR) gene. We then demonstrated that this region functions as a regulatory element through binding of the transcriptional repressor promyelocytic leukemia zinc finger protein (PLZF) at the rs12101261 site. Repression by PLZF depended on the rs12101261 disease susceptibility allele and was increased by IFNα. Intrathymic TSHR expression was decreased in individuals homozygous for the rs12101261 disease-associated genotype compared with carriers of the disease-protective allele. Our studies discovered a genetic-epigenetic interaction involving a noncoding SNP in the TSHR gene that regulates thymic TSHR gene expression and facilitates escape of TSHR-reactive T cells from central tolerance, triggering GD.
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KASL clinical practice guidelines: management of hepatitis C. Clin Mol Hepatol 2014; 20:89-136. [PMID: 25032178 PMCID: PMC4099340 DOI: 10.3350/cmh.2014.20.2.89] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Accepted: 05/20/2014] [Indexed: 12/16/2022] Open
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Kozielewicz D, Zaleśna A, Dybowska D. Can pegylated interferon α 2a cause development of thyroid disorders in patients with chronic hepatitis B? Expert Opin Drug Saf 2014; 13:1009-14. [DOI: 10.1517/14740338.2014.921156] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Abstract
Hashimoto thyroiditis (HT), now considered the most common autoimmune disease, was described over a century ago as a pronounced lymphoid goiter affecting predominantly women. In addition to this classic form, several other clinico-pathologic entities are now included under the term HT: fibrous variant, IgG4-related variant, juvenile form, Hashitoxicosis, and painless thyroiditis (sporadic or post-partum). All forms are characterized pathologically by the infiltration of hematopoietic mononuclear cells, mainly lymphocytes, in the interstitium among the thyroid follicles, although specific features can be recognized in each variant. Thyroid cells undergo atrophy or transform into a bolder type of follicular cell rich in mitochondria called Hürthle cell. Most HT forms ultimately evolve into hypothyroidism, although at presentation patients can be euthyroid or even hyperthyroid. The diagnosis of HT relies on the demonstration of circulating antibodies to thyroid antigens (mainly thyroperoxidase and thyroglobulin) and reduced echogenicity on thyroid sonogram in a patient with proper clinical features. The treatment remains symptomatic and based on the administration of synthetic thyroid hormones to correct the hypothyroidism as needed. Surgery is performed when the goiter is large enough to cause significant compression of the surrounding cervical structures, or when some areas of the thyroid gland mimic the features of a nodule whose cytology cannot be ascertained as benign. HT remains a complex and ever expanding disease of unknown pathogenesis that awaits prevention or novel forms of treatment.
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Fallahi P, Ferrari SM, Politti U, Giuggioli D, Ferri C, Antonelli A. Autoimmune and neoplastic thyroid diseases associated with hepatitis C chronic infection. Int J Endocrinol 2014; 2014:935131. [PMID: 25374602 PMCID: PMC4211174 DOI: 10.1155/2014/935131] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2014] [Accepted: 09/24/2014] [Indexed: 12/17/2022] Open
Abstract
Frequently, patients with hepatitis C virus (HCV) chronic infection have high levels of serum anti-thyroperoxidase and/or anti-thyroglobulin autoantibodies, ultrasonographic signs of chronic autoimmune thyroiditis, and subclinical hypothyroidism, in female gender versus healthy controls, or hepatitis B virus infected patients. In patients with "HCV-associated mixed cryoglobulinemia" (MC + HCV), a higher prevalence of thyroid autoimmune disorders was shown not only compared to controls, but also versus HCV patients without cryoglobulinemia. Patients with MC + HCV or HCV chronic infection show a higher prevalence of papillary thyroid cancer than controls, in particular in patients with autoimmune thyroiditis. Patients with HCV chronic infection, or with MC + HCV, in presence of autoimmune thyroiditis, show higher serum levels of T-helper (Th)1 (C-X-C motif) ligand 10 (CXCL10) chemokine, but normal levels of Th2 (C-C motif) ligand 2 chemokine, than patients without thyroiditis. HCV thyroid infection could act by upregulating CXCL10 gene expression and secretion in thyrocytes recruiting Th1 lymphocytes that secrete interferon-γ and tumor necrosis factor-α. These cytokines might induce a further CXCL10 secretion by thyrocytes, thus perpetuating the immune cascade, which may lead to the appearance of autoimmune thyroid disorders in genetically predisposed subjects. A careful monitoring of thyroid function, particularly where nodules occur, is recommended in HCV patients.
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Affiliation(s)
- Poupak Fallahi
- Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy
| | - Silvia Martina Ferrari
- Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy
| | - Ugo Politti
- Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy
| | - Dilia Giuggioli
- Department of Medical, Surgical, Maternal, Pediatric and Adult Sciences, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy
| | - Clodoveo Ferri
- Department of Medical, Surgical, Maternal, Pediatric and Adult Sciences, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy
| | - Alessandro Antonelli
- Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy
- *Alessandro Antonelli:
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Torino F, Barnabei A, Paragliola R, Baldelli R, Appetecchia M, Corsello SM. Thyroid dysfunction as an unintended side effect of anticancer drugs. Thyroid 2013; 23:1345-66. [PMID: 23750887 DOI: 10.1089/thy.2013.0241] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
BACKGROUND Several of the currently used anticancer drugs may variably affect thyroid function, with impairment ranging from modified total but not free concentration of thyroid hormones to overt thyroid disease. SUMMARY Cytotoxic agents seem to alter thyroid function in a relatively small proportion of adult patients. Anticancer hormone drugs may mainly alter serum levels of thyroid hormone-binding proteins without clinically relevant thyroid dysfunction. Old immunomodulating drugs, such as interferon-α and interleukin-2, are known to induce variably high incidence of autoimmune thyroid dysfunction. Newer immune checkpoint inhibitors, such as anti-CTLA4 monoclonal antibodies, are responsible for a relatively low incidence of thyroiditis and may induce secondary hypothyroidism resulting from hypophysitis. Central hypothyroidism is a well-recognized side effect of bexarotene. Despite their inherent selectivity, tyrosine kinase inhibitors may cause high rates of thyroid dysfunction. Notably, thyroid toxicity seems to be restricted to tyrosine kinase inhibitors targeting key kinase-receptors in angiogenic pathways, but not other kinase-receptors (e.g., epidermal growth factor receptors family or c-KIT). In addition, a number of these agents may also increase the levothyroxine requirement in thyroidectomized patients. CONCLUSIONS The pathophysiology of thyroid toxicity induced by many anticancer agents is not fully clarified and for others it remains speculative. Thyroid dysfunction induced by anticancer agents is generally manageable and dose reduction or discontinuation of these agents is not required. The prognostic relevance of thyroid autoimmunity, overt and subclinical hypothyroidism induced by anticancer drugs, the value of thyroid hormone replacement in individuals with abnormal thyrotropin following anticancer systemic therapy, and the correct timing of replacement therapy in cancer patients need to be defined more accurately in well-powered prospective clinical trials.
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Affiliation(s)
- Francesco Torino
- 1 Department of Systems Medicine, Tor Vergata University of Rome , Rome, Italy
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46
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Mavragani CP, Niewold TB, Chatzigeorgiou A, Danielides S, Thomas D, Kirou KA, Kamper E, Kaltsas G, Crow MK. Increased serum type I interferon activity in organ-specific autoimmune disorders: clinical, imaging, and serological associations. Front Immunol 2013; 4:238. [PMID: 23966997 PMCID: PMC3746787 DOI: 10.3389/fimmu.2013.00238] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2013] [Accepted: 08/02/2013] [Indexed: 01/27/2023] Open
Abstract
Background: Activation of the type I interferon (IFN) pathway has been implicated in the pathogenesis of systemic autoimmune disorders but its role in the pathogenesis of organ-specific autoimmunity is limited. We tested the hypothesis that endogenous expression of type I IFN functional activity contributes to the pathogenesis of autoimmune thyroid disease (ATD) and type I diabetes (T1DM). Methods: We studied 39 patients with ATD and 39 age and sex matched controls along with 88 T1DM patients and 46 healthy matched controls respectively. Available clinical and serological parameters were recorded by chart review, and thyroid ultrasound was performed in 17 ATD patients. Type I IFN serum activity was determined in all subjects using a reporter cell assay. The rs1990760 SNP of the interferon-induced helicase 1 gene was genotyped in ATD patients. Results: Serum type I IFN activity was increased in patients with ATD and T1DM compared to controls (p-values: 0.002 and 0.04, respectively). ATD patients with high type I IFN serum activity had increased prevalence of antibodies against thyroglobulin (anti-Tg) and cardiopulmonary manifestations compared to those with low IFN activity. Additionally, the presence of micronodules on thyroid ultrasound was associated with higher type I IFN levels. In patients with T1DM, high IFN levels were associated with increased apolipoprotein-B levels. Conclusion: Serum type I IFN activity is increased in ATD and T1DM and is associated with specific clinical, serological, and imaging features. These findings may implicate type I IFN pathway in the pathogenesis of specific features of organ-specific autoimmunity.
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Affiliation(s)
- Clio P Mavragani
- Mary Kirkland Center for Lupus Research, Hospital for Special Surgery , New York, NY , USA ; Department of Physiology, School of Medicine, University of Athens , Athens , Greece
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47
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Alsabbagh MEY, Eisa N, Alraiyes AH, Alraies MC. Chronic hepatitis C therapy: a rare complication revisited. BMJ Case Rep 2013; 2013:bcr-2013-200514. [PMID: 23893287 DOI: 10.1136/bcr-2013-200514] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
The combined regimen of peg-interferon α2a plus ribavirin along with protease inhibitors (boceprevir or telaprevir) is considered as a very portent and effective therapy for hepatitis C infections. However, this combined therapy has been associated with a side effect that can make the course of the disease more complicated. In this case, a 50-year-old man developed insulin-dependent diabetes soon after initiating triple hepatitis C therapy. The treatment had to be stopped and the course of his hepatitis C infection has been challenged with this rare side effect.
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48
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Hasham A, Zhang W, Lotay V, Haggerty S, Stefan M, Concepcion E, Dieterich DT, Tomer Y. Genetic analysis of interferon induced thyroiditis (IIT): evidence for a key role for MHC and apoptosis related genes and pathways. J Autoimmun 2013; 44:61-70. [PMID: 23683877 DOI: 10.1016/j.jaut.2013.04.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2013] [Revised: 03/22/2013] [Accepted: 04/01/2013] [Indexed: 12/18/2022]
Abstract
Autoimmune thyroid diseases (AITD) have become increasingly recognized as a complication of interferon-alpha (IFNα) therapy in patients with chronic Hepatitis C virus (HCV) infection. Interferon-induced thyroiditis (IIT) can manifest as clinical thyroiditis in approximately 15% of HCV patients receiving IFNα and subclinical thyroiditis in up to 40% of patients, possibly resulting in either dose reduction or discontinuation of IFNα treatment. However, the exact mechanisms that lead to the development of IIT are unknown and may include IFNα-mediated immune-recruitment as well as direct toxic effects on thyroid follicular cells. We hypothesized that IIT develops in genetically predisposed individuals whose threshold for developing thyroiditis is lowered by IFNα. Therefore, our aim was to identify the susceptibility genes for IIT. We used a genomic convergence approach combining genetic association data with transcriptome analysis of genes upregulated by IFNα. Integrating results of genetic association, transcriptome data, pathway, and haplotype analyses enabled the identification of 3 putative loci, SP100/110/140 (2q37.1), HLA (6p21.3), and TAP1 (6p21.3) that may be involved in the pathogenesis of IIT. Immune-regulation and apoptosis emerged as the predominant mechanisms underlying the etiology of IIT.
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Affiliation(s)
- Alia Hasham
- Division of Endocrinology, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA
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49
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Soldevila B, Alonso N, Martínez-Arconada MJ, Granada ML, Boada A, Vallejos V, Fraile M, Fernández-Sanmartín MA, Pujol-Borrell R, Puig-Domingo M, Sanmartí A, Martínez-Cáceres EM. Regulatory T cells and other lymphocyte subpopulations in patients with melanoma developing interferon-induced thyroiditis during high-dose interferon-α2b treatment. Clin Endocrinol (Oxf) 2013; 78:621-8. [PMID: 22957689 DOI: 10.1111/cen.12036] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2012] [Revised: 06/03/2012] [Accepted: 09/01/2012] [Indexed: 11/26/2022]
Abstract
CONTEXT One of the side effects of interferon-alpha therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT melanoma patients remains to be defined. OBJECTIVE Our objective was to assess different peripheral blood lymphocyte subpopulations, mainly regulatory T cells (Tregs), in melanoma patients who developed IIT. DESIGN, PATIENTS AND METHODS From 30 melanoma patients receiving high-dose interferon (HDI)-alpha 2b (IFN-α2b) treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-MM) and healthy controls (Co-H). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment and at appearance of IIT (TT). RESULTS Nine patients developed IIT (30%): four Hashimoto's thyroiditis and five destructive thyroiditis. An increase in Tregs was observed in both melanoma groups during HDI treatment. A decrease in CD3(+) , NKT lymphocyte subpopulations and Bcl2 expression on B cells was also observed in both groups. However, no changes were observed in the percentage of CD4(+) , CD8(+) , CD3(+) γδ(+) , CD19(+) , transitional B cells (CD24(high) CD38(high) CD19(+) CD27(-) ), natural killer (NK), invariant NKT (iNKT) lymphocytes and Th1/Th2 balance when BT was compared with ET. At TT, IIT patients had a higher Tregs percentage than Co-MM (P = 0·012) and Co-H (P = 0·004), a higher iNKT percentage than Co-MM (P = 0·011), a higher transitional B cells percentage than Co-H (P = 0·015), a lower CD3(+) percentage than Co-H (P = 0·001) and a lower Bcl2 expression on B cells than Co-H (P < 0·001). CONCLUSIONS Our results point to the immunomodulatory effects of IFN-α on different lymphocyte subpopulations and a possible role of Tregs in melanoma patients who developed IIT.
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Affiliation(s)
- Berta Soldevila
- Department of Endocrinology and Nutrition, Hospital Universitari Germans Trias i Pujol, Universitat Autonoma de Barcelona, spain.
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50
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Abstract
Autoimmune thyroid diseases (AITD), including Graves' disease and Hashimoto's thyroiditis, are among the commonest autoimmune disorders, affecting approximately 5 % of the population. Epidemiological data support strong genetic influences on the development of AITD. Since the identification of HLA-DR3 as a major AITD susceptibility gene, there have been significant advances made in our understanding of the genetic mechanisms leading to AITD. We have shown that an amino acid substitution of alanine or glutamine with arginine at position 74 in the HLA-DR peptide binding pocket is a critical factor in the development of AITD, and we are continuing to dissect these mechanisms at the molecular level. In addition to the MHC class II genes, there are now several other confirmed gene loci associated with AITD, including immune-regulatory (CD40, CTLA-4, PTPN22, FOXP3, and CD25) and thyroid-specific genes (thyroglobulin and TSHR). Mechanistically, it is postulated that susceptibility genes interact with certain environmental triggers to induce AITD through epigenetic effects. In this review, we summarize some of the recent advances made in our laboratory dissecting the genetic-epigenetic interactions underlying AITD. As shown in our recent studies, epigenetic modifications offer an attractive mechanistic possibility that can provide further insight into the etiology of AITD.
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Affiliation(s)
- Alia Hasham
- Division of Endocrinology, Department of Medicine, Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1055, New York, NY 10029, USA
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