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Chisca M, Larouche J, Xing Q, Kassiotis G. Antibodies against endogenous retroviruses. Immunol Rev 2024; 328:300-313. [PMID: 39152687 PMCID: PMC11659944 DOI: 10.1111/imr.13378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/19/2024]
Abstract
The human genome harbors hundreds of thousands of integrations of ancient retroviruses, amassed over millions of years of evolution. To reduce further amplification in the genome, the host prevents transcription of these now endogenous retroviruses (ERVs) through epigenetic repression and, with evolutionary time, ERVs are incapacitated by accumulating mutations and deletions. However, several members of recently endogenized ERV groups still retain the capacity to produce viral RNA, retroviral proteins, and higher order structures, including virions. The retention of viral characteristics, combined with the reversible nature of epigenetic repression, particularly as seen in cancer, allow for immunologically unanticipated ERV expression, perceived by the adaptive immune system as a genuine retroviral infection, to which it has to respond. Accordingly, antibodies reactive with ERV antigens have been detected in diverse disorders and, occasionally, in healthy individuals. Although they are part of self, the retroviral legacy of ERV antigens, and association with and, possibly, causation of disease states may set them apart from typical self-antigens. Consequently, the pathogenic or, indeed, host-protective capacity of antibodies targeting ERV antigens is likely to be context-dependent. Here, we review the immunogenicity of typical ERV proteins, with emphasis on the antibody response and its potential disease implications.
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Affiliation(s)
- Mihaela Chisca
- Retroviral Immunology LaboratoryThe Francis Crick InstituteLondonUK
| | | | - Qi Xing
- Retroviral Immunology LaboratoryThe Francis Crick InstituteLondonUK
| | - George Kassiotis
- Retroviral Immunology LaboratoryThe Francis Crick InstituteLondonUK
- Department of Infectious Disease, Faculty of MedicineImperial College LondonLondonUK
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Tatour M, Neeman Z, Aviv A, Hazzan R. Increased Risk of Non-Hodgkin Lymphoma in Autoimmune Hepatitis: A Large Retrospective Cohort Study. J Clin Med 2024; 13:6258. [PMID: 39458208 PMCID: PMC11508903 DOI: 10.3390/jcm13206258] [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: 07/26/2024] [Revised: 09/07/2024] [Accepted: 10/18/2024] [Indexed: 10/28/2024] Open
Abstract
Background/Objectives: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease caused by an autoimmune attack on hepatocytes. The first-line treatment for AIH comprises two core components: glucocorticoids and thiopurine analog inhibitors and mycophenolate mofetil (MMF). Numerous studies have suggested an increased risk for lymphoma among patients with either rheumatoid arthritis or inflammatory bowel disease (IBD) who are treated with azathioprine/6-mercaptopurine (6-MP). The relative risk of non-Hodgkin lymphoma (NHL) among autoimmune hepatitis patients treated with these immunosuppressive drugs remains unclear. We aimed at investigating the risk of NHL across a large retrospective AIH cohort after a long-term follow-up. Methods: This retrospective, population-based study comprised approximately 2.7 million adults over two decades. It included adult patients aged 20 years or older at the time of autoimmune hepatitis diagnosis who had initiated treatment with azathioprine, 6-MP, or MMF. The primary outcome was the development of non-Hodgkin lymphoma. Results: The study initially included 834 patients diagnosed with AIH. A total of 685 patients remained in the research cohort after matching the data to the local cancer registry. Compared to the predicted NHL rate in the general population, NHL incidence was considerably higher in AIH patients (Standardized Incidence Ratio, SIR = 36.5). Subgroup studies showed that lymphoma mainly affected patients 45 years of age and over and was detected primarily during the first seven years following the AIH diagnosis. No correlation was found between the incidence of NHL and the treatment drug used. Conclusions: Patients with AIH exhibit a markedly higher risk of NHL compared to the general population.
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Affiliation(s)
- Mifleh Tatour
- Clalit Health Services, Nof Hagalil 1710601, Israel;
- Department of Family Medicine, Clalit Health Services, Afula 1710601, Israel
| | - Ziv Neeman
- Imaging Institute & Nuclear Medicine, Emek Medical Center, Clalit Health Services, Afula 183411, Israel;
- Ruth and Bruce Rappaport, Faculty of Medicine, Technion—Institute of Technology, Haifa 3109601, Israel;
| | - Ariel Aviv
- Ruth and Bruce Rappaport, Faculty of Medicine, Technion—Institute of Technology, Haifa 3109601, Israel;
- Hematology Unit, HaEmek Medical Center, Afula 183411, Israel
| | - Rawi Hazzan
- Clalit Health Services, Nof Hagalil 1710601, Israel;
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel
- Emek Medical Center, 21 Yitzhak Rabin Blvd, Afula 183411, Israel
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Ventelä J, Alanko A, Auvinen A, Lohi O, Nikkilä A. Dual direction associations between common autoimmune diseases and leukemia among children and young adults: A systematic review. Cancer Epidemiol 2023; 86:102411. [PMID: 37423102 DOI: 10.1016/j.canep.2023.102411] [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: 05/17/2023] [Revised: 06/28/2023] [Accepted: 06/29/2023] [Indexed: 07/11/2023]
Abstract
BACKGROUND Childhood leukemia and many autoimmune (AI) diseases are severe pediatric conditions with lifelong consequences. AI diseases form a heterogeneous disease group affecting about 5 % of children worldwide, while leukemia is the most common malignancy among children aged 0-14 years. The timing and similarities in suggested inflammatory and infectious triggers of AI disease and leukemia have raised a question whether the diseases share common etiological origins. We conducted a systematic review to evaluate the evidence linking childhood leukemia and AI diseases. DATA SOURCES In the systematic literature search CINAHL (from 1970), Cochrane Library (form 1981), PubMed (from 1926) and Scopus (from 1948) were queried in June 2023. REVIEW METHODS We included studies covering the association between any AI disease and acute leukemia, limiting it to children and adolescents under 25 years old. The studies were reviewed independently by two researchers and the risk of bias was assessed. RESULTS A total of 2119 articles were screened and 253 studies were selected for detailed evaluation. Nine studies met the inclusion criteria, of which eight were cohort studies and one was a systematic review. The diseases covered were type 1 diabetes mellitus, inflammatory bowel diseases and juvenile arthritis alongside acute leukemia. Five cohort studies were suitable for more detailed analysis: a rate ratio for leukemia diagnosis after any AI disease was 2.46 (95 % CI 1.17-5.18; heterogeneity I2 15 %) with a random-effects model. CONCLUSIONS The results of this systematic review indicate that AI diseases in childhood are associated with a moderately increased risk of leukemia. The association for individual AI diseases needs further investigation.
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Affiliation(s)
- Julia Ventelä
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
| | - Anni Alanko
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Anssi Auvinen
- Faculty of Social Sciences, Tampere University and Tampere University Hospital, Tampere, Finland
| | - Olli Lohi
- Tampere Center for Child, Adolescent, Maternal Health Research and Tays Cancer Center, Tampere University and Tampere University Hospital, Tampere, Finland
| | - Atte Nikkilä
- Tampere Center for Child, Adolescent, Maternal Health Research and Tays Cancer Center, Tampere University and Tampere University Hospital, Tampere, Finland
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Alehashemi S, Ward MM. Risk of Hematologic Malignancies in Elderly Patients With Ankylosing Spondylitis: A Cohort Study and Systematic Review. Mayo Clin Proc 2023; 98:100-110. [PMID: 36470752 PMCID: PMC9822846 DOI: 10.1016/j.mayocp.2022.06.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 05/09/2022] [Accepted: 06/30/2022] [Indexed: 12/04/2022]
Abstract
OBJECTIVE To examine the risk of hematologic malignancies in older adults with ankylosing spondylitis (AS). PATIENTS AND METHODS We used US Medicare data from January 1, 1999, to December 31, 2010, to identify a population-based cohort of beneficiaries with AS. We also included beneficiaries with inflammatory bowel disease (IBD) as disease controls and beneficiaries without AS or IBD as unaffected controls. We excluded those treated with tumor necrosis factor inhibitors in this period. We followed up each group for new diagnosis claims for hematologic malignancies until September 30, 2015. RESULTS We included 12,451 beneficiaries with AS, 234,905 with IBD, and 10,975,340 unaffected controls, with a mean follow-up of 9.9, 9.3, and 8.0 years, respectively. We identified 297 hematologic malignancies in the AS group, 4538 malignancies in the IBD group, and 128,239 malignancies in unaffected controls. The standardized incidence ratio in AS vs unaffected controls was 1.39 (95% CI, 1.05 to 1.61) for non-Hodgkin lymphoma, 1.50 (95% CI, 1.17 to 1.92) for chronic lymphocytic leukemia, and 1.52 (95% CI, 1.12 to 2.06) for multiple myeloma. Risks of acute myeloid leukemia and chronic myeloid leukemia were not elevated in AS, and there were too few cases of Hodgkin lymphoma to compute risks. Risks were comparable to those of beneficiaries with IBD. We also performed a systematic literature review of the risk of hematologic malignancy in AS, focusing on age associations, which have not been previously examined. We identified 21 studies in the systematic literature review, which included mainly young or middle-aged patients. Results suggested that AS was largely not associated with an increased risk of hematologic malignancies. Two cohort studies reported an increased risk of multiple myeloma in AS. CONCLUSION The risks of non-Hodgkin lymphoma, chronic lymphocytic leukemia, and multiple myeloma are increased among elderly patients with AS.
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MESH Headings
- Middle Aged
- Humans
- Aged
- United States/epidemiology
- Multiple Myeloma/complications
- Cohort Studies
- Leukemia, Lymphocytic, Chronic, B-Cell/epidemiology
- Leukemia, Lymphocytic, Chronic, B-Cell/complications
- Spondylitis, Ankylosing/complications
- Spondylitis, Ankylosing/drug therapy
- Spondylitis, Ankylosing/epidemiology
- Medicare
- Hematologic Neoplasms/complications
- Lymphoma, Non-Hodgkin/epidemiology
- Lymphoma, Non-Hodgkin/etiology
- Lymphoma, Non-Hodgkin/pathology
- Inflammatory Bowel Diseases/complications
- Inflammatory Bowel Diseases/drug therapy
- Inflammatory Bowel Diseases/epidemiology
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Affiliation(s)
- Sara Alehashemi
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
| | - Michael M Ward
- Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD
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Yu Y, Liu JL, Tian DS. Anti-N-methyl-D-aspartate receptor encephalitis associated with chronic myelogenous leukemia, causality or coincidence? A case report. BMC Neurol 2022; 22:153. [PMID: 35461209 PMCID: PMC9034597 DOI: 10.1186/s12883-022-02675-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 04/12/2022] [Indexed: 11/10/2022] Open
Abstract
Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most frequent autoimmune paraneoplastic encephalitis, and is primarily associated with ovarian teratomas. Here, we report the first case of a patient diagnosed with chronic myelogenous leukemia (CML) during the recovery phase of anti-NMDAR encephalitis. Case presentation The patient was admitted with fever, headache, and seizures. Brain MRI revealed a cerebrospinal fluid (CSF)-containing arachnoid cyst in the left temporal lobe with no other abnormal signals. EEG showed diffuse background slowing in the delta-theta range. The patient tested positive for anti-NMDAR antibodies in both the serum and CSF. One year after the onset of encephalitis, the patient was referred to the Department of Hematology for extreme leukocytosis. Karyotype analysis showed the presence of Philadelphia chromosome t(9;22)(q34;q11). Quantitative reverse transcriptase PCR analysis further identified BCR/ABL1 fusion transcripts; thus, CML was diagnosed. Conclusions To the best of our knowledge, this is the first case of anti-NMDAR encephalitis associated with CML. This report should alert clinicians to consider CML as a malignancy that is possibly associated with limbic encephalitis.
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Zhong H, Liu S, Wang Y, Xu D, Li M, Zhao Y, Zeng X. Primary Sjögren's syndrome is associated with increased risk of malignancies besides lymphoma: A systematic review and meta-analysis. Clin Exp Rheumatol 2022; 21:103084. [PMID: 35341972 DOI: 10.1016/j.autrev.2022.103084] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Accepted: 03/23/2022] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Patients with primary Sjögren's syndrome(pSS) have increased risk of non-Hodgkin lymphoma (NHL). However, whether pSS patients have increased risk of other malignancies is unclear. The aim of this study is to investigate the association between pSS and the risk of malignancy, with a focus on hematological malignancies besides lymphoma and solid tumors through a systematic review and meta-analysis. METHOD We searched PubMed and EMBASE by March 21st 2021. Inclusion criteria were as follows: (1) pSS was the exposure of interest; (2) newly developed malignancies were the outcome of interest; (3) standardized incidence ratio or relative risk with 95% confidence interval or essential data to calculate them were reported. (4) Study design was cohort study. Patient with other connective diseases were excluded. Quality assessment was conducted according to Newcastle-Ottawa Scale for cohort study. Random or fixed effect models were used to calculate the pooled SIR according to heterogeneity measured by I2. RESULTS A total of 1003 articles were found by a comprehensive search in PubMed and EMBASE. Twenty-eight articles were eligible. Four of them were from the same database, the one with longest observational span was chosen. Therefore, twenty-five articles were included for final analysis, which involved more than 47,607 pSS patients with the follow-up of more than 452,468 person-year. We found that pSS was significantly associated with increased risks of overall malignancy(pooled SIR 2.17, 95%1.57-3.00), hematological malignancy(pooled SIR 11.55, 95%CI 4.32-30.90) including NHL(pooled SIR 13.71, 95%CI 8.83-21.29), Hodgkin lymphoma(pooled SIR 8.84, 95%CI 5.00-15.61), multiple myeloma(pooled SIR 8.27, 95%CI 3.08-22.24), leukemia(pooled SIR 2.56, 95%CI 1.78-3.69) and solid tumors(pooled SIR 1.39, 95%CI 0.90-2.13) including lung cancer(pooled SIR 1.55, 95%CI 1.29-1.85), thyroid cancer(pooled SIR 2.05, 95%CI 1.20-3.48), non-melanoma skin cancer(pooled SIR 1.71, 95%CI 1.08-2.72), kidney/urinary tract cancer(pooled SIR 1.36, 95%CI 1.02; 1.81), liver cancer(pooled SIR 1.70, 95%CI 1.13-2.57) and prostate cancer(pooled SIR 1.50, 95%CI 1.02-2.22). CONCLUSION This meta-analysis showed that pSS patients had increased risk of overall cancer, which not only contributed by NHL, but also by other hematological malignancies and solid tumors.
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Affiliation(s)
- Hui Zhong
- Department of Rheumatology and Clinical Immunology of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Siyao Liu
- Department of Rheumatology and Clinical Immunology of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Yanhong Wang
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, PR China
| | - Dong Xu
- Department of Rheumatology and Clinical Immunology of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
| | - Mengtao Li
- Department of Rheumatology and Clinical Immunology of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
| | - Yan Zhao
- Department of Rheumatology and Clinical Immunology of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Xiaofeng Zeng
- Department of Rheumatology and Clinical Immunology of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
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Scandolara TB, Pacholak LM, Tavares IM, Kern R, Garcia-Velazquez L, Panis C. Cross talks between autoimmunity and cancer. TRANSLATIONAL AUTOIMMUNITY 2022:15-49. [DOI: 10.1016/b978-0-323-85415-3.00005-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Zaccardelli A, Liu X, Ford JA, Cui J, Lu B, Chu SH, Schur PH, Speyer CB, Costenbader KH, Robinson WH, Sokolove J, Karlson EW, Camargo CA, Sparks JA. Elevated Anti-Citrullinated Protein Antibodies Prior to Rheumatoid Arthritis Diagnosis and Risks for Chronic Obstructive Pulmonary Disease or Asthma. Arthritis Care Res (Hoboken) 2021; 73:498-509. [PMID: 31961487 PMCID: PMC7371499 DOI: 10.1002/acr.24140] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 01/07/2020] [Indexed: 01/04/2023]
Abstract
OBJECTIVE To investigate elevation of anti-citrullinated protein antibodies (ACPAs) before diagnosis of rheumatoid arthritis (RA) and risks for chronic obstructive pulmonary disease (COPD) or asthma. METHODS We performed a matched cohort study nested within the Nurses' Health Studies among women who donated blood. Women with incident RA after blood draw (self-reported, then confirmed by medical records) were each matched to 3 controls by age, cohort, year, and menopausal factors. Pre-RA ACPA positivity was defined as >99th percentile of control distribution by a research assay or by cyclic citrullinated peptide in a subset. Incident COPD and asthma after index date (date of blood draw) were identified by questionnaires. Cox regression estimated hazard ratios (HRs) for incident COPD or asthma (in separate analyses) associated with pre-RA, pre-RA ACPA+, or pre-RA ACPA- phenotypes each compared to their matched non-RA controls. RESULTS We analyzed 283 women who were pre-RA and 842 controls; blood was donated a mean ± SD of 9.7 ± 5.8 years before RA diagnosis. Fifty-nine women (20.8%) were pre-RA ACPA+. There were 107 cases of incident COPD and 105 incident asthma cases during 21,489 person-years of follow-up. Pre-RA ACPA+ was associated with increased COPD risk (HR 3.04 [95% confidence interval (95% CI) 1.33-7.00]) after adjusting for covariates including smoking pack-years. Pre-RA ACPA+ had an HR for asthma of 1.74 (multivariable 95% CI 0.72-4.24), similar to the risk of asthma for pre-RA ACPA- (HR 1.65 [95% CI 1.11-2.46]). CONCLUSION Women with elevated ACPA before RA diagnosis had increased risk for developing COPD compared to controls. Women who later developed RA were more likely to develop asthma than controls, regardless of pre-RA ACPA status.
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Affiliation(s)
| | - Xinyi Liu
- Brigham and Women’s Hospital, Boston, MA, USA
| | - Julia A. Ford
- Brigham and Women’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Jing Cui
- Brigham and Women’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Bing Lu
- Brigham and Women’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Su H. Chu
- Brigham and Women’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Peter H. Schur
- Brigham and Women’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | | | - Karen H. Costenbader
- Brigham and Women’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - William H. Robinson
- Stanford University School of Medicine, Palo Alto, CA, USA
- VA Palo Alto Health Care System, Palo Alto, CA, USA
| | - Jeremy Sokolove
- Stanford University School of Medicine, Palo Alto, CA, USA
- VA Palo Alto Health Care System, Palo Alto, CA, USA
- GlaxoSmithKline
| | - Elizabeth W. Karlson
- Brigham and Women’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Carlos A. Camargo
- Brigham and Women’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
- Massachusetts General Hospital, Boston, MA, USA
| | - Jeffrey A. Sparks
- Brigham and Women’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
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The risk of leukemia in patients with rheumatoid arthritis: a systematic review and meta-analysis. Clin Rheumatol 2020; 40:1283-1289. [PMID: 32939570 DOI: 10.1007/s10067-020-05396-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 08/18/2020] [Accepted: 09/12/2020] [Indexed: 10/23/2022]
Abstract
OBJECTIVES The relationship between rheumatoid arthritis (RA) and the risk of leukemia was still controversial. This study aimed to assess the risk of leukemia in patients with rheumatoid arthritis by systematic review and meta-analysis. METHODS Relevant studies were identified by searching PubMed, Embase, Cochrane Library, and SinoMed up to December 2019. Random effects model analysis was used to pool standardized incidence ratios (SIRs) and 95% confidence interval. RESULTS A total of 15 relevant studies that met the criteria were included. Compared with the general population, patients with RA showed an increased risk of leukemia (SIR = 1.51, 95% CI: 1.34-1.70). The statistical heterogeneity was moderate with an I2 of 55.5%. In subgroup analysis, the source of heterogeneity may be due to differences in sample size. Publication bias was not found in the Begg funnel plot and the Egger test. CONCLUSION Our findings suggested that the risk of leukemia in RA was increased compared with the general population. Key points • This is the first systematic review and meta-analysis to assess the risk of leukemia in RA. • Our study suggested that the risk of leukemia in RA was increased compared with the general population. • This study indicated that the risk of leukemia in RA was higher in non-Asian populations.
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Risk of cancer in multiple sclerosis (MS): A systematic review and meta-analysis. Autoimmun Rev 2020; 19:102650. [PMID: 32801049 DOI: 10.1016/j.autrev.2020.102650] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Accepted: 02/29/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVE To assess the pooled risk of cancer in patients with multiple sclerosis. METHODS We searched PubMed, Scopus, EMBASE, Web of Science, Ovid, google scholar and gray literature (references of studies, conference abstracts) which were published up to September 2019. The search strategy included the MeSH and text words as ((cancer) OR tumor) OR neoplasm) OR "malignant neoplasm) OR "benign neoplasm) AND (Multiple Sclerosis OR Sclerosis, Multiple) OR Sclerosis, Disseminated) OR Disseminated Sclerosis) OR MS (Multiple Sclerosis)) OR Multiple Sclerosis, Acute Fulminating). RESULTS The first literature search revealed 18,996 articles. After deletion of duplicate articles, finally, 264 articles remained. Excluding non-relevant articles, resulted in including 5 articles which met inclusion criteria. The RR estimated between 0.7 and 1.67 in included articles. The pooled RR estimated as 0.83 (95% CI:0.73-0.96) (I2 = 90%, P < 0.001). Two studies provided prevalence of different cancers. The pooled prevalence of breast cancer in two studies was 2% (95%CI:2%-2%) (I2 = 0%). The pooled prevalence of digestive system cancer in two studies was 2% (95%CI:1%-2%) (I2 = 0%). The pooled prevalence of skin cancer in two studies was 1% (95%CI:0%-1%) (I2 = 0). CONCLUSION The result of this systematic review showed that the risk of cancer in patients with MS is less than the general population.
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Hemminki K, Huang W, Sundquist J, Sundquist K, Ji J. Autoimmune diseases and hematological malignancies: Exploring the underlying mechanisms from epidemiological evidence. Semin Cancer Biol 2020; 64:114-121. [DOI: 10.1016/j.semcancer.2019.06.005] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Revised: 06/04/2019] [Accepted: 06/06/2019] [Indexed: 02/08/2023]
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Liu Z, Mahale P, Engels EA. Sepsis and Risk of Cancer Among Elderly Adults in the United States. Clin Infect Dis 2020; 68:717-724. [PMID: 29982318 DOI: 10.1093/cid/ciy530] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Accepted: 06/27/2018] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Sepsis is an important cause of mortality among older adults in the United States. The association between sepsis and subsequent risk of cancer is poorly understood. METHODS Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, we conducted a case-control study in US adults. We included 1801156 cases with a first cancer diagnosis in SEER during 1992-2013 (ages 66-115 years) and 200000 cancer-free controls from a 5% random sample of Medicare beneficiaries. Sepsis was identified using inpatient Medicare claims. Associations with sepsis were estimated using logistic regression. RESULTS After correction for multiple comparisons, sepsis was significantly associated with increased risk for cancers of the colon (adjusted odds ratio [aOR] = 1.12), rectum (1.13), liver (1.47), lung (1.17), and cervix (1.52), as well as acute myeloid leukemia (AML, 1.19), chronic myeloid leukemia (1.54), and myelodysplastic syndrome (1.30). Inverse associations were observed for cancers of the breast (aOR = 0.86), prostate (0.75), kidney (0.90), and thyroid (0.68) and for melanoma (0.83), diffuse large B-cell lymphoma (0.89), and follicular lymphoma (0.65). Sepsis was significantly associated with the following 9 types of cancer in the period >5 years following sepsis diagnosis: thyroid, prostate, colon, rectum, lung, and liver and follicular lymphoma, melanoma, and AML. CONCLUSIONS Sepsis is associated with increased or decreased risks for a small group of cancers. Factors that may explain these associations include etiologic effects. Other associations may reflect the presence of precursor conditions or patterns in ascertainment of cancer and screening.
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Affiliation(s)
- Zhiwei Liu
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
| | - Parag Mahale
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
| | - Eric A Engels
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
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Zheng G, Chattopadhyay S, Sud A, Sundquist K, Sundquist J, Försti A, Houlston R, Hemminki A, Hemminki K. Second primary cancers in patients with acute lymphoblastic, chronic lymphocytic and hairy cell leukaemia. Br J Haematol 2019; 185:232-239. [DOI: 10.1111/bjh.15777] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Accepted: 12/12/2018] [Indexed: 12/29/2022]
Affiliation(s)
- Guoqiao Zheng
- Division of Molecular Genetic Epidemiology German Cancer Research Centre (DKFZ) Heidelberg Germany
- Faculty of Medicine University of Heidelberg Heidelberg Germany
| | - Subhayan Chattopadhyay
- Division of Molecular Genetic Epidemiology German Cancer Research Centre (DKFZ) Heidelberg Germany
- Faculty of Medicine University of Heidelberg Heidelberg Germany
| | - Amit Sud
- Division of Molecular Genetic Epidemiology German Cancer Research Centre (DKFZ) Heidelberg Germany
- Division of Genetics and Epidemiology The Institute of Cancer Research London UK
| | - Kristina Sundquist
- Centre for Primary Health Care Research Lund University Malmö Sweden
- Department of Family Medicine and Community Health Department of Population Health Science and Policy Icahn School of Medicine at Mount Sinai New York NY USA
- Centre for Community‐based Healthcare Research and Education (CoHRE) Department of Functional Pathology School of Medicine Shimane University Matsue Japan
| | - Jan Sundquist
- Centre for Primary Health Care Research Lund University Malmö Sweden
- Department of Family Medicine and Community Health Department of Population Health Science and Policy Icahn School of Medicine at Mount Sinai New York NY USA
- Centre for Community‐based Healthcare Research and Education (CoHRE) Department of Functional Pathology School of Medicine Shimane University Matsue Japan
| | - Asta Försti
- Division of Molecular Genetic Epidemiology German Cancer Research Centre (DKFZ) Heidelberg Germany
- Centre for Primary Health Care Research Lund University Malmö Sweden
| | - Richard Houlston
- Division of Genetics and Epidemiology The Institute of Cancer Research London UK
- Division of Molecular Pathology The Institute of Cancer Research London UK
| | - Akseli Hemminki
- Cancer Gene Therapy Group Faculty of Medicine University of Helsinki Helsinki Finland
- Comprehensive Cancer Centre Helsinki University Hospital Helsinki Finland
| | - Kari Hemminki
- Division of Molecular Genetic Epidemiology German Cancer Research Centre (DKFZ) Heidelberg Germany
- Centre for Primary Health Care Research Lund University Malmö Sweden
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14
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Di Marco M, Ramassone A, Pagotto S, Anastasiadou E, Veronese A, Visone R. MicroRNAs in Autoimmunity and Hematological Malignancies. Int J Mol Sci 2018; 19:ijms19103139. [PMID: 30322050 PMCID: PMC6213554 DOI: 10.3390/ijms19103139] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Accepted: 10/02/2018] [Indexed: 12/13/2022] Open
Abstract
Autoimmunity and hematological malignancies are often concomitant in patients. A causal bidirectional relationship exists between them. Loss of immunological tolerance with inappropriate activation of the immune system, likely due to environmental and genetic factors, can represent a breeding ground for the appearance of cancer cells and, on the other hand, blood cancers are characterized by imbalanced immune cell subsets that could support the development of the autoimmune clone. Considerable effort has been made for understanding the proteins that have a relevant role in both processes; however, literature advances demonstrate that microRNAs (miRNAs) surface as the epigenetic regulators of those proteins and control networks linked to both autoimmunity and hematological malignancies. Here we review the most up-to-date findings regarding the miRNA-based molecular mechanisms that underpin autoimmunity and hematological malignancies.
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Affiliation(s)
- Mirco Di Marco
- Ageing Research Center and Translational medicine-CeSI-MeT, 66100 Chieti, Italy.
- Department of Medical, Oral and Biotechnological Sciences (DSMOB), "G. d'Annunzio" University Chieti-Pescara, 66100 Chieti, Italy.
| | - Alice Ramassone
- Ageing Research Center and Translational medicine-CeSI-MeT, 66100 Chieti, Italy.
- Department of Medical, Oral and Biotechnological Sciences (DSMOB), "G. d'Annunzio" University Chieti-Pescara, 66100 Chieti, Italy.
| | - Sara Pagotto
- Ageing Research Center and Translational medicine-CeSI-MeT, 66100 Chieti, Italy.
- Department of Medical, Oral and Biotechnological Sciences (DSMOB), "G. d'Annunzio" University Chieti-Pescara, 66100 Chieti, Italy.
| | - Eleni Anastasiadou
- Harvard Medical School Initiative for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
| | - Angelo Veronese
- Ageing Research Center and Translational medicine-CeSI-MeT, 66100 Chieti, Italy.
- Department of Medicine and Aging Science (DMSI), "G. d'Annunzio" University Chieti-Pescara, 66100 Chieti, Italy.
| | - Rosa Visone
- Ageing Research Center and Translational medicine-CeSI-MeT, 66100 Chieti, Italy.
- Department of Medical, Oral and Biotechnological Sciences (DSMOB), "G. d'Annunzio" University Chieti-Pescara, 66100 Chieti, Italy.
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15
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Hemminki K, Försti A, Sundquist K, Sundquist J, Li X. Familial associations of lymphoma and myeloma with autoimmune diseases. Blood Cancer J 2017; 7:e515. [PMID: 28157190 PMCID: PMC5301032 DOI: 10.1038/bcj.2016.123] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Revised: 11/08/2016] [Accepted: 11/28/2016] [Indexed: 11/09/2022] Open
Abstract
Many B-cell neoplasms are associated with autoimmune diseases (AIDs) but most evidence is based on a personal rather than a family history of AIDs. Here we calculated risks for non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL) and multiple myeloma (MM) when family members were diagnosed with any of 44 different AIDs, or, independently, risk for AIDs when family members were diagnosed with a neoplasm. A total of 64 418 neoplasms and 531 155 AIDs were identified from Swedish nationwide health care records. NHL was associated with a family history of five AIDs, all increasing the risk, HL was associated with one AID increasing and three AIDs decreasing the risk while MM had no association. A family history of NHL was associated with eight, HL with seven and MM with seven different AIDs, nine increasing and 13 decreasing the risk. The present family data on B-cell neoplasms and AIDs show an approximately equal number of associations for risk increase and risk decrease, suggesting that inherited genes or gene-environment interactions may increase the risk or be protective. These results differed from published data on personal history of AID, which only report increased risks, often vastly higher and for different AIDs compared with the present data.
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Affiliation(s)
- K Hemminki
- Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Center for Primary Health Care Research, Lund University, Malmö, Sweden
| | - A Försti
- Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Center for Primary Health Care Research, Lund University, Malmö, Sweden
| | - K Sundquist
- Center for Primary Health Care Research, Lund University, Malmö, Sweden.,Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA
| | - J Sundquist
- Center for Primary Health Care Research, Lund University, Malmö, Sweden.,Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA
| | - X Li
- Center for Primary Health Care Research, Lund University, Malmö, Sweden
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16
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Hemminki K, Liu X, Ji J, Försti A. Origin of B-Cell Neoplasms in Autoimmune Disease. PLoS One 2016; 11:e0158360. [PMID: 27355450 PMCID: PMC4927111 DOI: 10.1371/journal.pone.0158360] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Accepted: 06/14/2016] [Indexed: 11/18/2022] Open
Abstract
Autoimmune diseases (ADs) are associated with a number of B-cell neoplasms but the associations are selective in regard to the type of neoplasm and the conferred risks are variable. So far no mechanistic bases for these differential associations have been demonstrated. We speculate that developmental origin of B-cells might propose a mechanistic rationale for their carcinogenic response to autoimmune stimuli and tested the hypothesis on our previous studies on the risks of B-cell neoplasms after any of 33 ADs. We found that predominantly germinal center (GC)-derived B-cells showed multiple associations with ADs: diffuse large B cell lymphoma associated with 15 ADs, follicular lymphoma with 7 ADs and Hodgkin lymphoma with 11 ADs. Notably, these neoplasms shared significant associations with 5 ADs (immune thrombocytopenic purpura, polymyositis/dermatomyositis, rheumatoid arthritis, Sjogren syndrome and systemic lupus erythematosis). By contrast, primarily non-GC neoplasms, acute lymphocytic leukemia, chronic lymphocytic leukemia and myeloma associated with 2 ADs only and mantle cell lymphoma with 1 AD. None of the neoplasms shared associated ADs. These data may suggest that autoimmune stimulation critically interferes with the rapid cell division, somatic hypermutation, class switch recombination and immunological selection of maturing B-cell in the GC and delivers damage contributing to transformation.
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Affiliation(s)
- Kari Hemminki
- Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120, Heidelberg, Germany
- Center for Primary Health Care Research, Lund University, 205 02, Malmö, Sweden
- * E-mail:
| | - Xiangdong Liu
- Center for Primary Health Care Research, Lund University, 205 02, Malmö, Sweden
- Department of Measles, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Jianguang Ji
- Center for Primary Health Care Research, Lund University, 205 02, Malmö, Sweden
| | - Asta Försti
- Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120, Heidelberg, Germany
- Center for Primary Health Care Research, Lund University, 205 02, Malmö, Sweden
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17
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Gunnarsson N, Höglund M, Stenke L, Wållberg-Jonsson S, Sandin F, Björkholm M, Dreimane A, Lambe M, Markevärn B, Olsson-Strömberg U, Wadenvik H, Richter J, Själander A. Increased prevalence of prior malignancies and autoimmune diseases in patients diagnosed with chronic myeloid leukemia. Leukemia 2016; 30:1562-7. [PMID: 27080811 DOI: 10.1038/leu.2016.59] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2015] [Revised: 02/11/2016] [Accepted: 02/19/2016] [Indexed: 02/03/2023]
Abstract
We recently reported an increased incidence of second malignancies in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKI). To elucidate whether this increase may be linked, not to TKI but rather to a hereditary or acquired susceptibility to develop cancer, we estimated the prevalence of malignancies, autoimmune disease (AD) and chronic inflammatory disease (CID) in CML patients prior to their CML diagnosis. Nationwide population-based registers were used to identify patients diagnosed with CML in Sweden 2002-2012 and to estimate the prevalence of other malignancies, AD and CID prior to their CML diagnosis. For each patient with CML, five matched controls were selected from the general population. Conditional logistic regression was used to calculate odds ratios (OR). Nine hundred and eighty-four CML patients were assessed, representing more than 45 000 person-years of follow-up. Compared with matched controls, the prevalence of prior malignancies and AD was elevated in CML patients: OR 1.47 (95% confidence interval (CI) 1.20-1.82) and 1.55 (95% CI 1.21-1.98), respectively. No associations were detected between CML and previous CID. An increased prevalence of other malignancies and AD prior to the diagnosis of CML suggest that a hereditary or acquired predisposition to cancer and/or autoimmunity is involved in the pathogenesis of CML.
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Affiliation(s)
- N Gunnarsson
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - M Höglund
- Department of Medical Science and Division of Hematology, University Hospital, Uppsala, Sweden
| | - L Stenke
- Department of Hematology, Karolinska University Hospital and Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - S Wållberg-Jonsson
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - F Sandin
- Regional Cancer Centre, Uppsala-Örebro, Sweden
| | - M Björkholm
- Department of Hematology, Karolinska University Hospital and Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - A Dreimane
- Department of Hematology, University Hospital, Linköping, Sweden
| | - M Lambe
- Regional Cancer Centre, Uppsala-Örebro, Sweden.,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - B Markevärn
- Department of Hematology, University Hospital, Umeå, Sweden
| | - U Olsson-Strömberg
- Department of Medical Science and Division of Hematology, University Hospital, Uppsala, Sweden
| | - H Wadenvik
- Department of Hematology, Sahlgrenska University Hospital, Göteborg, Sweden
| | - J Richter
- Department of Hematology and Vascular Disorders, Skåne University Hospital, Lund, Sweden
| | - A Själander
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
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18
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Lam GY, Halloran BP, Peters AC, Fedorak RN. Lymphoproliferative disorders in inflammatory bowel disease patients on immunosuppression: Lessons from other inflammatory disorders. World J Gastrointest Pathophysiol 2015; 6:181-192. [PMID: 26600976 PMCID: PMC4644882 DOI: 10.4291/wjgp.v6.i4.181] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Accepted: 09/28/2015] [Indexed: 02/06/2023] Open
Abstract
Immunosuppressive agents, such as thiopurines, methotrexate, and biologics, have revolutionized the treatment of inflammatory bowel disease (IBD). However, a number of case reports, case control studies and retrospective studies over the last decade have identified a concerning link between immunosuppression and lymphoproliferative disorders (LPDs), the oncological phenomenon whereby lymphocytes divide uncontrollably. These LPDs have been associated with Epstein-Barr virus (EBV) infection in which the virus provides the impetus for malignant transformation while immunosuppression hampers the immune system’s ability to detect and clear these malignant cells. As such, the use of immunosuppressive agents may come at the cost of increased risk of developing LPD. While little is known about the LPD risk in IBD, more is known about immunosuppression in the post-transplantation setting and the development of EBV associated post-transplantation lymphoproliferative disorders (PTLD). In review of the PTLD literature, evidence is available to demonstrate that certain immune suppressants such as cyclosporine and T-lymphocyte modulators in particular are associated with an increased risk of PTLD development. As well, high doses of immunosuppressive agents and multiple immunosuppressive agent use are also linked to increased PTLD development. Here, we discuss these findings in context of IBD and what future studies can be taken to understand and reduce the risk of EBV-associated LPD development from immunosuppression use in IBD.
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19
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Wiersma VR, Michalak M, Abdullah TM, Bremer E, Eggleton P. Mechanisms of Translocation of ER Chaperones to the Cell Surface and Immunomodulatory Roles in Cancer and Autoimmunity. Front Oncol 2015; 5:7. [PMID: 25688334 PMCID: PMC4310273 DOI: 10.3389/fonc.2015.00007] [Citation(s) in RCA: 106] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Accepted: 01/10/2015] [Indexed: 01/12/2023] Open
Abstract
Endoplasmic reticulum (ER) chaperones (e.g., calreticulin, heat shock proteins, and isomerases) perform a multitude of functions within the ER. However, many of these chaperones can translocate to the cytosol and eventually the surface of cells, particularly during ER stress induced by e.g., drugs, UV irradiation, and microbial stimuli. Once on the cell surface or in the extracellular space, the ER chaperones can take on immunogenic characteristics, as mostly described in the context of cancer, appearing as damage-associated molecular patterns recognized by the immune system. How ER chaperones relocate to the cell surface and interact with other intracellular proteins appears to influence whether a tumor cell is targeted for cell death. The relocation of ER proteins to the cell surface can be exploited to target cancer cells for elimination by immune mechanism. Here we evaluate the evidence for the different mechanisms of ER protein translocation and binding to the cell surface and how ER protein translocation can act as a signal for cancer cells to undergo killing by immunogenic cell death and other cell death pathways. The release of chaperones can also exacerbate underlying autoimmune conditions, such as rheumatoid arthritis and multiple sclerosis, and the immunomodulatory role of extracellular chaperones as potential cancer immunotherapies requires cautious monitoring, particularly in cancer patients with underlying autoimmune disease.
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Affiliation(s)
- Valerie R. Wiersma
- Department of Surgery, Translational Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Marek Michalak
- University of Exeter Medical School, Exeter Devon, UK
- Department of Biochemistry, University of Alberta, Edmonton, AB, Canada
| | | | - Edwin Bremer
- Department of Surgery, Translational Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- University of Exeter Medical School, Exeter Devon, UK
| | - Paul Eggleton
- University of Exeter Medical School, Exeter Devon, UK
- Department of Biochemistry, University of Alberta, Edmonton, AB, Canada
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20
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Marrie RA, Cohen J, Stuve O, Trojano M, Sørensen PS, Reingold S, Cutter G, Reider N. A systematic review of the incidence and prevalence of comorbidity in multiple sclerosis: overview. Mult Scler 2015; 21:263-81. [PMID: 25623244 PMCID: PMC4361468 DOI: 10.1177/1352458514564491] [Citation(s) in RCA: 281] [Impact Index Per Article: 28.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Background: Comorbidity is an area of increasing interest in multiple sclerosis (MS). Objective: The objective of this review is to estimate the incidence and prevalence of comorbidity in people with MS and assess the quality of included studies. Methods: We searched the PubMed, SCOPUS, EMBASE and Web of Knowledge databases, conference proceedings, and reference lists of retrieved articles. Two reviewers independently screened abstracts. One reviewer abstracted data using a standardized form and the abstraction was verified by a second reviewer. We assessed study quality using a standardized approach. We quantitatively assessed population-based studies using the I2 statistic, and conducted random-effects meta-analyses. Results: We included 249 articles. Study designs were variable with respect to source populations, case definitions, methods of ascertainment and approaches to reporting findings. Prevalence was reported more frequently than incidence; estimates for prevalence and incidence varied substantially for all conditions. Heterogeneity was high. Conclusion: This review highlights substantial gaps in the epidemiological knowledge of comorbidity in MS worldwide. Little is known about comorbidity in Central or South America, Asia or Africa. Findings in North America and Europe are inconsistent. Future studies should report age-, sex- and ethnicity-specific estimates of incidence and prevalence, and standardize findings to a common population.
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Affiliation(s)
- Ruth Ann Marrie
- Department of Internal Medicine, University of Manitoba, Canada/Department of Community Health Sciences, University of Manitoba, Health Sciences Center, Canada
| | - Jeffrey Cohen
- Mellen Center for MS Treatment and Research, Cleveland Clinic, USA
| | - Olaf Stuve
- Department of Neurology and Neurotherapeutics, University of Texas Southwestern, USA
| | - Maria Trojano
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Italy
| | | | | | - Gary Cutter
- Department of Biostatistics, University of Alabama at Birmingham, USA
| | - Nadia Reider
- Department of Internal Medicine, University of Manitoba, Canada
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21
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Marrie RA, Reider N, Cohen J, Stuve O, Trojano M, Sorensen PS, Reingold SC, Cutter G. A systematic review of the incidence and prevalence of cancer in multiple sclerosis. Mult Scler 2014; 21:294-304. [PMID: 25533302 PMCID: PMC4429168 DOI: 10.1177/1352458514564489] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Studies of cancer incidence and prevalence in multiple sclerosis (MS) have produced conflicting results. OBJECTIVE To estimate the incidence and prevalence of cancer in persons with MS and review the quality of included studies. METHODS We searched the PUBMED, SCOPUS, Web of Knowledge, and EMBASE databases, conference proceedings, and reference lists of all articles retrieved. Abstracts were screened for relevance by two reviewers. Data from included articles were captured using a standardized form, and the abstraction was verified by a second reviewer. We assessed quality of the included studies. We quantitatively assessed studies using the I (2) statistic, and conducted meta-analyses for population-based studies. RESULTS We identified 38 studies. Estimates for incidence and prevalence varied substantially for most cancers. In population-based studies, cervical, breast, and digestive cancers had the highest incidence. The risk of meningiomas and urinary system cancers appeared higher than expected, while the risks of pancreatic, ovarian, prostate and testicular cancer were lower than expected. CONCLUSION The complexity of understanding cancer risk in MS is augmented by inconsistencies in study design, and the relative paucity of age, sex and ethnicity-specific risk estimates from which the strong impact of age on the incidence of cancers can be assessed.
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Affiliation(s)
- Ruth Ann Marrie
- Department of Internal Medicine, University of Manitoba, Winnipeg, Canada/Department of Community Health Sciences, University of Manitoba, Winnipeg, Canada
| | - Nadia Reider
- Department of Internal Medicine, University of Manitoba, Winnipeg, Canada
| | - Jeffrey Cohen
- Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, OH, USA
| | - Olaf Stuve
- Department of Neurology and Neurotherapeutics, University of Texas Southwestern, Dallas, TX, USA
| | - Maria Trojano
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Italy
| | | | | | - Gary Cutter
- Department of Biostatistics, University of Alabama at Birmingham, USA
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22
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Fallah M, Liu X, Ji J, Försti A, Sundquist K, Hemminki K. Autoimmune diseases associated with non-Hodgkin lymphoma: a nationwide cohort study. Ann Oncol 2014; 25:2025-2030. [DOI: 10.1093/annonc/mdu365] [Citation(s) in RCA: 134] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
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Fallah M, Liu X, Ji J, Försti A, Sundquist K, Hemminki K. Hodgkin lymphoma after autoimmune diseases by age at diagnosis and histological subtype. Ann Oncol 2014; 25:1397-1404. [PMID: 24718892 DOI: 10.1093/annonc/mdu144] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/08/2023] Open
Abstract
BACKGROUND Increased risk of Hodgkin lymphoma (HL) associated with personal history of several autoimmune diseases (ADs), such as rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, and immune thrombocytopenic purpura, are known. Whether there are other HL-related ADs and whether the increased risk of HL after ADs holds across sex, age, year of diagnosis, or HL histological subtype is unclear. PATIENTS AND METHODS We systematically analyzed the risk of HL in 878 161 Swedish patients diagnosed with 33 different ADs in 1964-2010. During ∼10-year follow-up of ADs patients, 371 incident HL cases were diagnosed. RESULTS Significantly increased overall standardized incidence ratio (SIR) for HL after ADs was 2.0 (95% confidence interval: 1.8-2.2); AD-specific SIRs: autoimmune hemolytic anemia 19.9 (7.2-43.6), sarcoidosis 10.3 (7.8-13.4), systemic lupus erythematosus 8.4 (5.2-12.9), immune thrombocytopenic purpura 7.0 (3.2-13.3), polyarteritis nodosa 6.6 (1.2-19.5), polymyositis/dermatomyositis 6.3 (2.0-14.9), Behcet's disease 5.6 (2.7-10.3), Sjögren's syndrome 5.0 (2.1-9.8), rheumatoid arthritis 3.2 (2.6-3.9), polymyalgia rheumatica 2.2 (1.4-3.5), and psoriasis 1.9 (1.3-2.6). Men with AD had slightly higher risk of HL (2.4, 2.0-2.7) compared with women (1.8, 1.5-2.0). Only 23% of ADs were diagnosed before age 35 years and the overall SIR for HL diagnosis before age 35 [1.4, (1.0-1.8)] was lower than that in older ages [35 ≤ age < 50: 2.1 (1.6-2.7); age ≥ 50: 2.2 (2.0-2.5)], except for sarcoidosis [age < 35: 19.3 (10.5-32.5); 35 ≤ age < 50: 10.4 (5.7-17.5); age ≥ 50: 8.4 (5.6-12.1)]. Risks of all classical HLs significantly increased after ADs: lymphocyte depletion 3.7 (1.5-7.6), lymphocyte-rich 3.7 (2.3-5.9), mixed cellularity 2.4 (1.8-3.2), and nodular sclerosis 1.7 (1.3-2.1). CONCLUSION Several, but not all ADs (11/33), had a positive association with all classical histological subtypes of HL. Higher risks of classical HL after polyarteritis nodosa, polymyositis/dermatomyositis, Behcet's disease, Sjögren's syndrome, polymyalgia rheumatica, and psoriasis were novel findings of this study.
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Affiliation(s)
- M Fallah
- Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
| | - X Liu
- Center for Primary Health Care Research, Lund University, Malmö, Sweden
| | - J Ji
- Center for Primary Health Care Research, Lund University, Malmö, Sweden
| | - A Försti
- Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Center for Primary Health Care Research, Lund University, Malmö, Sweden
| | - K Sundquist
- Center for Primary Health Care Research, Lund University, Malmö, Sweden
| | - K Hemminki
- Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Center for Primary Health Care Research, Lund University, Malmö, Sweden
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25
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Andersen CL, Lindegaard H, Vestergaard H, Siersma VD, Hasselbalch HC, de Fine Olivarius N, Bjerrum OW, Junker P. Risk of lymphoma and solid cancer among patients with rheumatoid arthritis in a primary care setting. PLoS One 2014; 9:e99388. [PMID: 24914777 PMCID: PMC4051682 DOI: 10.1371/journal.pone.0099388] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2014] [Accepted: 05/14/2014] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND Several studies have demonstrated an association between rheumatoid arthritis (RA) and lymphoproliferative malignancies, but pathogenic mechanisms remain unclear. We investigated 1) the risk of lymphoproliferative malignancies and solid tumors in adults with RA identified in primary care and 2) the possible mediating role of blood eosinophilia in the clonal evolution of cancer in these patients. METHODS From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356,196 individuals with at least one differential cell count (DIFF) encompassing the eosinophil count between 2000-2007. From these, one DIFF was randomly chosen (the index DIFF). By linking to the Danish National Patient Register, we categorized the selected individuals according to known longstanding (≥3 years) or recent onset (<3 years) RA prior to the index DIFF. In addition, the cohort was stratified according to management in primary or secondary care. From the Danish Cancer Registry we ascertained malignancies within four years following the index DIFF. Using multivariable logistic regression, odds ratios (OR) were calculated and adjusted for sex, age, year, month, eosinophilia, comorbid conditions and C-reactive protein (CRP). RESULTS 921 patients had recent onset RA and 2,578 had longer disease duration. Seventy three percent of RA patients were managed in primary care. After adjustment for sex, age, year, and month, neither recent onset nor long-standing RA was associated with incident lymphoproliferative malignancies or solid cancers. These risk estimates did not change when eosinophilia, CRP, and comorbidities were included in the models. CONCLUSIONS In this large cohort of patients with RA of short or long duration recruited from a primary care resource, RA was not associated with an increased risk of lymphoproliferative or solid cancers during 4 years of follow-up, when the models were adjusted for confounders. Blood eosinophilia could not be identified as a mediator of cancer development in the present setting.
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Affiliation(s)
- Christen Lykkegaard Andersen
- Department of Hematology, Roskilde University Hospital, Roskilde, Denmark
- The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
- * E-mail:
| | - Hanne Lindegaard
- Department of Rheumatology, Odense University Hospital, Odense, Denmark
| | - Hanne Vestergaard
- Department of Hematology, Odense University Hospital, Odense, Denmark
| | - Volkert Dirk Siersma
- The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | | | - Niels de Fine Olivarius
- The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Ole Weis Bjerrum
- Department of Hematology, Copenhagen University Hospital, Copenhagen, Denmark
| | - Peter Junker
- Department of Rheumatology, Odense University Hospital, Odense, Denmark
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Kim JW, Pyo JH, Kim KJ, Kim H, Jeoung Y, Ji JD, Lee YH. Acute Precursor T Cell Lymphoblastic Leukemia Associated with Behcet's Disease: A Case Report. JOURNAL OF RHEUMATIC DISEASES 2014. [DOI: 10.4078/jrd.2014.21.1.46] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Ji Won Kim
- Division of Rheumatology, Department of Internal Medicine, Korea University Medical College, Seoul, Korea
| | - Jeung Hui Pyo
- Division of Rheumatology, Department of Internal Medicine, Korea University Medical College, Seoul, Korea
| | - Kyeong Jin Kim
- Division of Rheumatology, Department of Internal Medicine, Korea University Medical College, Seoul, Korea
| | - Ho Kim
- Division of Rheumatology, Department of Internal Medicine, Korea University Medical College, Seoul, Korea
| | - Yong Jeoung
- Division of Rheumatology, Department of Internal Medicine, Korea University Medical College, Seoul, Korea
| | - Jong Dae Ji
- Division of Rheumatology, Department of Internal Medicine, Korea University Medical College, Seoul, Korea
| | - Young Ho Lee
- Division of Rheumatology, Department of Internal Medicine, Korea University Medical College, Seoul, Korea
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Abstract
Acute leukaemias are a group of malignancies characterised by the invasion of the bone marrow by immature haematopoietic precursors and differentiation arrest at various maturation steps. Multiplicity of intrinsic and extrinsic factors influences the transformation and progression of leukaemia. The intrinsic factors encompass genetic alterations of cellular pathways leading to the activation of, among others, inflammatory pathways (such as nuclear factor kappa B). The extrinsic components include, among others, the inflammatory pathways activated by the bone marrow microenvironment and include chemokines, cytokines and adhesion molecules. In this chapter, we review the role of inflammatory processes in the transformation, survival and proliferation of leukaemias, particularly the role of nuclear factor kappa B and its downstream signalling in leukaemias and the novel therapeutic strategies that exploit potentially unique properties of inflammatory signalling that offer interesting options for future therapeutic interventions.
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