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Priora M, Realmuto C, Parisi S, Ditto MC, Borrelli R, Peroni CL, Laganà A, Fusaro E. Rheumatologic manifestations of hepatitis C in the era of direct-acting antiviral agents. MINERVA GASTROENTERO 2020; 66:280-289. [PMID: 32218427 DOI: 10.23736/s1121-421x.20.02680-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Beyond the classic hepatic complications, hepatitis C (HCV) infection is considered as a systemic disease, since extrahepatic manifestations become clinically evident in 40% to 70% of the patients and it can frequently include rheumatic ones. Furthermore, HCV can promote the production of several autoantibodies, thus complicating the differential diagnosis between primitive and HCV-related rheumatic disorders. The recent development of direct-acting antivirals (DAA) against HCV has revolutionized the field, reducing the damage stemming from systemic inflammatory phenomena and persistent immune activation associated with continuous HCV replication. Our review focuses on the main rheumatologic manifestations associated with chronic HCV infection as well as the impact of DAA interferon-free treatments on such extrahepatic clinical involvement.
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Affiliation(s)
- Marta Priora
- Division of Rheumatology, Città della Salute e della Scienza, University of Turin, Turin, Italy -
| | - Cristina Realmuto
- Division of Rheumatology, Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Simone Parisi
- Division of Rheumatology, Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Maria C Ditto
- Division of Rheumatology, Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Richard Borrelli
- Division of Rheumatology, Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Clara L Peroni
- Division of Rheumatology, Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Angela Laganà
- Division of Rheumatology, Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Enrico Fusaro
- Division of Rheumatology, Città della Salute e della Scienza, University of Turin, Turin, Italy
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Navarta LM, Espul CA, Acosta-Rivero N. High prevalence of a variety of autoantibodies in a population of hepatitis C virus-infected individuals. APMIS 2018; 126:515-522. [PMID: 29924449 DOI: 10.1111/apm.12850] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 04/24/2018] [Indexed: 12/11/2022]
Abstract
Hepatitis C virus (HCV) infection has been related to self-reactivity, extrahepatic manifestations and autoimmune diseases. The main goals of this work were to study the prevalence of autoantibodies and their relationship with viral titers and biochemical markers of hepatic damage in patients infected with HCV. Autoantibodies (ANA, AMA, SMA, APC, LKM, DNAds, ANCA, ATG and RF) were determined in 73 individuals with chronic HCV infection and 44 healthy volunteers. The presence of these antibodies was related to demographic variables, viral titers and biochemical parameters. A high prevalence of autoantibodies, particularly for RF, that was associated with female gender was observed in HCV-infected patients. In addition, SMA, ANA and ATG showed increased frequencies in HCV infection. Interestingly, the concurrent detection of SMA and more than one autoantibody was associated with high gGT levels. Notably, concurrent higher gGT, HCV and SMA levels were observed in male patients as compared to their female counterparts. These results indicate a relationship between HCV infection and the concurrent detection of various autoantibodies in the absence of symptoms of autoimmune diseases. They also suggest a link among the presence of a variety of autoantibodies simultaneously with SMA, increased gGT levels and HCV titers in a population of male patients.
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Affiliation(s)
| | | | - Nelson Acosta-Rivero
- Centre for Protein Studies, Department of Biochemistry, Faculty of Biology, University of Havana, Havana, Cuba
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Abstract
Cryoglobulins are immunoglobulins that undergo reversible precipitation at low temperatures. They can induce systemic vasculitis, characterized by purpuric cutaneous lesions, arthritis, peripheral neuropathy, hypocomplementemia and glomerular disease. Renal pathology reveals membranoproliferative glomerulonephritis, with particularly intense mesangial cell proliferation and infiltration by macrophages, associated with intracapillary thrombi. This renal disease presents as a nephritic syndrome, with heavy proteinuria, haematuria severe hypertension and rapidly progressive kidney failure that can lead to end-stage renal disease. Hepatitis C is the main cause of mixed (type 2 or 3) cryoglobulinemia and requires the initiation of a specific antiviral therapy, together with immunosuppressive drugs. Rituximab is now considered as the best immunosuppressive therapy in this situation, inducing B-cell depletion, clearance of circulating cryoglobulin and resolution of renal symptoms. Monoclonal (type 1) cryoglobulinemia, is a rare condition, but it usually reveals an B-cell or a plasma cell proliferation, that require a specific hematological treatment to obtain remission of the renal disease.
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Affiliation(s)
- Antonio Ponzetto
- Department of Internal Medicine, University of Turin, Turin, Italy
| | - Guido Carloni
- Istituto Farmacologia Traslazionale, Consiglio Nazionale delle Ricerche, Rome, Italy
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Boglione L, Cusato J, Allegra S, Cariti G, Di Perri G, D'Avolio A. Role of IL28B genotyping in patients with hepatitis C virus-associated mixed cryoglobulinemia and response to PEG-IFN and ribavirin treatment. Arch Virol 2015; 160:2009-17. [PMID: 26060059 DOI: 10.1007/s00705-015-2482-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Accepted: 05/30/2015] [Indexed: 12/11/2022]
Abstract
The role of interleukin (IL) 28B in the treatment of chronic hepatitis C (CHC) has recently been examined in many studies, while a possible relationship between IL28B and the presence of mixed cryoglobulinemia (MC) remains to be clarified. In this study, we analyzed the influence of IL28B rs8099917/rs12979860 on the presence of MC and the role in treatment with PEG-IFN. We retrospectively examined 541 patients affected by CHC who were treated with pegylated interferon (PEG-IFN) and ribavirin from 2003 to 2012. We included all treatment-naïve patients without other viral co-infections or major contraindications to the PEG-IFN and ribavirin standard of care. One hundred seventy-five patients (32.3 %) had MC; 49 of these (33.3 %) had symptomatic MC. The IL28B rs8099917/rs12979860 TT/CC genotype was the most frequent in MC-positive patients with sustained virological response (SVR) (p < 0.001), while the TG/TC genotype was most frequent in non-SVR (p < 0.001). The TT/CC genotype was found to be the main positive predictive factor of MC in HCV patients (OR = 11.914; IQR = 7.092-18.776; p < 0.001); HCV genotype 2/3 was the strongest positive predictive factor of SVR (OR = 10.448; IQR = 8.352-21.561; p < 0.001); IL28B rs8099917/rs12979860 TT/CC was a better predictive factor than rs12979860 CC alone (OR = 9.829 vs. 2.663). Negative predictive factors were Metavir score F3-F4 (OR = 0.625; IQR = 0.416-0.779; p = 0.008), insulin-resistance (OR = 0.315; IQR = 0.224-0.585; p < 0.001) and presence of symptoms (OR = 0.716; IQR = 0.492-0.855; p < 0.001). IL28B rs8099917/rs12979860 is useful in the treatment of MC-positive HCV patients with PEG-IFN and ribavirin; the TT/CC genotype is associated with SVR, the TG/TC with non-SVR; TT/CC is also predictive of MC in HCV patients.
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Affiliation(s)
- Lucio Boglione
- Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Turin, Italy,
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Calvaruso V, Craxì A. Immunological alterations in hepatitis C virus infection. World J Gastroenterol 2013; 19:8916-8923. [PMID: 24379616 PMCID: PMC3870544 DOI: 10.3748/wjg.v19.i47.8916] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2013] [Accepted: 11/13/2013] [Indexed: 02/06/2023] Open
Abstract
A higher prevalence of immunological processes has recently been reported in patients with hepatitis C virus (HCV) infection, focusing the attention of physicians and researchers on the close association between HCV and immune disorders. HCV lymphotropism represents the most important step in the pathogenesis of virus-related immunological diseases and experimental, virologic, and clinical evidence has demonstrated a trigger role for HCV both in systemic autoimmune diseases, such as rheumatoid arthritis, Sjögren syndrome, hemolytic anemia and severe thrombocytopenia, and in organ-specific autoimmune diseases, such as autoimmune hepatitis, thyroid disorders and diabetes. This review will outline the principal aspects of such HCV-induced immunological alterations, focusing on the prevalence of these less characterized HCV extrahepatic manifestations.
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El-attar EA, younes TB, Abdo SA, Riad GS. A study of serum levels of B cell-attracting chemokine-13 (CXCL 13) and rheumatologic manifestations of chronic hepatitis C virus infection in a cohort of Egyptian patients. ALEXANDRIA JOURNAL OF MEDICINE 2013. [DOI: 10.1016/j.ajme.2013.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
Affiliation(s)
- Enas Abdallah El-attar
- Physical Medicine, Rheumatology & Rehabilitation Departments , Ain Shams University , Faculty of Medicine , Egypt
| | - Takwa Badr younes
- Physical Medicine, Rheumatology & Rehabilitation Departments , Ain Shams University , Faculty of Medicine , Egypt
| | - Samia Ali Abdo
- Internal Medicine Departments, Ain Shams University , Faculty of Medicine , Egypt
| | - George Safwat Riad
- Internal Medicine Departments, Ain Shams University , Faculty of Medicine , Egypt
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Extrahepatic manifestations and autoantibodies in patients with hepatitis C virus infection. Clin Dev Immunol 2012. [PMID: 22988469 DOI: 10.1155/2012/871401]] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Patients with chronic hepatitis C virus (HCV) infection frequently have many extrahepatic manifestations, as persistent HCV infection often triggers lymphoproliferative disorders and metabolic abnormalities. These manifestations primarily include autoimmune disorders such as cryoglobulinemia, Sjögren's syndrome, and autoimmune thyroid disorders. It has been well established that chronic HCV infection plays important roles in the production of non-organ-specific autoantibodies, including antinuclear antibodies and smooth muscle antibodies, and organ-specific autoantibodies such as thyroid autoantibodies. However, the clinical significance of autoantibodies associated with the extrahepatic manifestations caused by HCV infection has not been fully recognized. In this paper, we mainly focus on the relationship between extrahepatic manifestations and the emergence of autoantibodies in patients with HCV infection and discuss the clinical relevance of the autoantibodies in the extrahepatic disorders.
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Himoto T, Masaki T. Extrahepatic manifestations and autoantibodies in patients with hepatitis C virus infection. Clin Dev Immunol 2012; 2012:871401. [PMID: 22988469 PMCID: PMC3440923 DOI: 10.1155/2012/871401] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2012] [Revised: 06/13/2012] [Accepted: 06/13/2012] [Indexed: 12/17/2022]
Abstract
Patients with chronic hepatitis C virus (HCV) infection frequently have many extrahepatic manifestations, as persistent HCV infection often triggers lymphoproliferative disorders and metabolic abnormalities. These manifestations primarily include autoimmune disorders such as cryoglobulinemia, Sjögren's syndrome, and autoimmune thyroid disorders. It has been well established that chronic HCV infection plays important roles in the production of non-organ-specific autoantibodies, including antinuclear antibodies and smooth muscle antibodies, and organ-specific autoantibodies such as thyroid autoantibodies. However, the clinical significance of autoantibodies associated with the extrahepatic manifestations caused by HCV infection has not been fully recognized. In this paper, we mainly focus on the relationship between extrahepatic manifestations and the emergence of autoantibodies in patients with HCV infection and discuss the clinical relevance of the autoantibodies in the extrahepatic disorders.
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Affiliation(s)
- Takashi Himoto
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, Japan.
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10
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Extrahepatic manifestations and autoantibodies in patients with hepatitis C virus infection. Clin Dev Immunol 2012. [PMID: 22988469 DOI: 10.1155/2012/871401].] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Patients with chronic hepatitis C virus (HCV) infection frequently have many extrahepatic manifestations, as persistent HCV infection often triggers lymphoproliferative disorders and metabolic abnormalities. These manifestations primarily include autoimmune disorders such as cryoglobulinemia, Sjögren's syndrome, and autoimmune thyroid disorders. It has been well established that chronic HCV infection plays important roles in the production of non-organ-specific autoantibodies, including antinuclear antibodies and smooth muscle antibodies, and organ-specific autoantibodies such as thyroid autoantibodies. However, the clinical significance of autoantibodies associated with the extrahepatic manifestations caused by HCV infection has not been fully recognized. In this paper, we mainly focus on the relationship between extrahepatic manifestations and the emergence of autoantibodies in patients with HCV infection and discuss the clinical relevance of the autoantibodies in the extrahepatic disorders.
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Abdel Fattah NSA, Hassan HE, Galal ZA, El Okda ESE. Assessment of anti-cyclic citrullinated peptide in psoriatic arthritis. BMC Res Notes 2009; 2:44. [PMID: 19298673 PMCID: PMC2666753 DOI: 10.1186/1756-0500-2-44] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2009] [Accepted: 03/19/2009] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Anti-cyclic citrullinated peptides (anti-CCP) are highly specific diagnostic and prognostic markers for rheumatoid arthritis (RA). They have been also found in psoriatic arthritis (PsA), with controversies as regards clinical and radiological associations. The current study assessed anti-CCP in PsA and determined its clinical and radiological associations. METHODS Four groups contributed to this study. 40 PsA, 40 psoriasis without arthritis, 40 RA and 40 healthy controls. They were tested for anti-CCP. Clinical and radiological data were collected and statistically compared between anti-CCP-positive and -negative PsA patients. RESULTS Seven PsA (17.5%) and 34 RA (85%) were seropositive for anti-CCP. Patients of other groups were anti-CCP-negative. Regarding anti-CCP concentrations, highly significant difference existed between different groups and between anti-CCP-positive and -negative PsA. Significantly higher numbers of involved, swollen and tender joints, deformities and functional impairment of peripheral joints and radiological changes were found in anti-CCP-positive PsA. CONCLUSION Anti-CCP may be found in PsA and are associated with higher number of involved, swollen and tender joints, with deformities and functional impairment of peripheral joints and with erosive arthritis.
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Affiliation(s)
- Nermeen S A Abdel Fattah
- Department of Dermatology and Venereology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
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12
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Abstract
Cryoglobulinemia are immune complexes that may induce systemic cryoglobulinemic vasculitis, a small-vessel vasculitis involving the skin, the joints, the peripheral nerve system, and the kidneys. During the last 15 years, progresses have been done after the discovery of the hepatitis C virus, the main cause of cryoglobulins. Main factors associated with cryoglobulin production are female gender, alcohol intake above 50 g/day, extensive liver fibrosis, and steatosis. Symptomatic cryoglobulins (i.e., vasculitis) are associated with older age, longer duration of infection, and main characteristics of cryoglobulin (type II, IgM kappa, high serum levels). The physiopathology is complex, and it involves humoral immunity, B- and T-cellular immunity but not the virus itself. Peg-Interféron alpha Ribavirine combination leads to a virological and clinical response of the vasculitis in about 70% of patients. In nonresponders, recent open series suggested the efficacy of Rituximab with a good response in up to 80% of patients but a relapse in 42% after 7 months after the last infusion. For future prospects and projects, new therapeutic strategies include a combination of best antiviral treatment with Peg-Interferon plus Ribavirin and Rituximab. Multicenter controlled trials are mandatory.
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Stefanova-Petrova DV, Tzvetanska AH, Naumova EJ, Mihailova AP, Hadjiev EA, Dikova RP, Vukov MI, Tchernev KG. Chronic hepatitis C virus infection: Prevalence of extrahepatic manifestations and association with cryoglobulinemia in Bulgarian patients. World J Gastroenterol 2007; 13:6518-28. [PMID: 18161922 PMCID: PMC4611291 DOI: 10.3748/wjg.v13.i48.6518] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the prevalence of extrahepatic manifestations in Bulgarian patients with chronic hepatitis C virus (HCV) infection and identify the clinical and biological manifestations associated with cryoglobulinemia.
METHODS: The medical records of 136 chronically infected HCV patients were reviewed to assess the prevalence of extrahepatic manifestations. Association between cryoglobulin-positivity and other manifestations were identified using χ2 and Fisher’s exact test. Risk factors for the presence of extrahepatic manifestations were assessed by logistic regression analysis.
RESULTS: Seventy six percent (104/136) of the patients had at least one extrahepatic manifestation. Clinical manifestations included fatigue (59.6%), kidney impairment (25.0%), type 2 diabetes (22.8%), paresthesia (19.9%), arthralgia (18.4%), palpable purpura (17.6%), lymphadenopathy (16.2%), pulmonary fibrosis (15.4%), thyroid dysfunction (14.7%), Raynaud’s phenomenon (11.8%), B-cell lymphoma (8.8%), sicca syndrome (6.6%), and lichen planus (5.9%). The biological manifestations included cryoglobulin production (37.5%), thrombocytopenia (31.6%), and autoantibodies: anti-nuclear (18.4%), anti-smooth muscle (16.9%), anti-neutrophil cytoplasm (13.2%) and anti-cardiolipin (8.8%). All extrahepatic manifestations showed an association with cryoglobulin-positivity, with the exception of thyroid dysfunction, sicca syndrome, and lichen planus. Risks factors for the presence of extrahepatic manifestations (univariate analysis) were: age ≥ 60 years, female gender, virus transmission by blood transfusions, longstanding infection (≥ 20 years), and extensive liver fibrosis. The most significant risks factors (multivariate analysis) were longstanding infection and extensive liver fibrosis.
CONCLUSION: We observed a high prevalence of extrahepatic manifestations in patients with chronic HCV infection. Most of these manifestations were associated with impaired lymphoproliferation and cryoglobulin production. Longstanding infection and extensive liver fibrosis were significant risk factors for the presence of extrahepatic manifestations in HCV patients.
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Bizzaro N. Antibodies to citrullinated peptides: a significant step forward in the early diagnosis of rheumatoid arthritis. Clin Chem Lab Med 2007; 45:150-7. [PMID: 17311500 DOI: 10.1515/cclm.2007.027] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
AbstractThe early diagnosis of rheumatoid arthritis (RA) has become a priority owing to the availability of effective disease-modifying agents that can improve patient wellbeing and influence the clinical outcome. However, this represents a real challenge, as no clinical, radiological or immunological features are pathognomonic at the time of presentation. For this reason, development of the anti-cyclic citrullinated peptide (CCP) antibody assay, a highly disease-specific serological marker for RA, has been a great step forward for the rheumatologist and the clinical laboratory. Over recent years, this test has increased in popularity and many studies have been performed. This review briefly considers the most recent data on the diagnostic accuracy of the CCP test, the genetic background that predisposes to antibody production, the diagnostic, prognostic and predictive values, and the clinical use of the assay in patients with RA.Clin Chem Lab Med 2007;45:150–7.
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Affiliation(s)
- Nicola Bizzaro
- Laboratorio di Patologia Clinica, Ospedale Civile, Tolmezzo, Italy.
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Nijenhuis S, Zendman AJW, Vossenaar ER, Pruijn GJM, vanVenrooij WJ. Autoantibodies to citrullinated proteins in rheumatoid arthritis: clinical performance and biochemical aspects of an RA-specific marker. Clin Chim Acta 2005; 350:17-34. [PMID: 15530456 DOI: 10.1016/j.cccn.2004.07.016] [Citation(s) in RCA: 77] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2004] [Revised: 06/30/2004] [Accepted: 07/15/2004] [Indexed: 12/01/2022]
Abstract
Rheumatoid arthritis (RA) is a common, systemic autoimmune disease of which the exact etiology is not known. In the past 10 years, substantial progress has been made in the identification of the antigens specifically recognized by the autoantibodies of RA patients. A central factor in this respect is citrullination, a form of post-translational modification that is strongly associated with autoimmunity in RA. Here, we summarize and discuss our current knowledge on (i) autoantibody systems in RA, (ii) the occurrence of peptidylarginine deiminases and (iii) citrullinated proteins in natural and diseased environments, and (iv) genetic factors involved in RA that may influence the generation and presentation of citrullinated proteins and the resulting antibody production against these modified proteins. Citrullination of proteins may play a key role in the initiation and/or the progression of RA. The onset of citrulline-specific autoimmunity in RA is probably mediated by both environmental and genetic factors, and future studies will learn whether therapeutic intervention at the level of citrullination may provide new possibilities to treat RA.
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Affiliation(s)
- Suzanne Nijenhuis
- Department of Biochemistry 161, Radboud University Nijmegen, PO Box 9101, NL-6500 HB Nijmegen, The Netherlands
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de Dios García-Díaz J, García-Sánchez M, Busteros JI, Arcos P. Polyarteritis nodosa after interferon treatment for chronic hepatitis C. J Clin Virol 2005; 32:181-2. [PMID: 15653424 DOI: 10.1016/j.jcv.2004.10.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/02/2004] [Indexed: 11/19/2022]
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Abstract
The hepatitis C virus (HCV) infection is a worldwide disease that is characterized by a preferential chronic evolution with mild to severe liver disease, including cirrhosis and, in lesser proportion, hepatocarcinoma. Out of these complications, HCV is frequently reported to complicate extrahepatic manifestations. Among those associated to HCV infection with a high degree of certainty, mixed cryoglobulinemia and its complications (skin, neurological, renal, rheumatological involvement) are the most prevalent (50%) in HCV-infected patients. The other diseases include noncryoglobulinemic systemic vasculitis, splenic lymphoma with villous lymphocytes, fatigue, porphyria cutanea tarda, sicca syndrome, and autoantibodies production. The extrahepatic manifestations that share mild-degree certainty of association with HCV infection include B-cell non-Hodgkin lymphoma, autoimmune thrombocytopenia, pruritus, and type II diabetes mellitus. The other diseases such as autoimmune thyroiditis, lichen planus are more questionable for their eventual association with HCV and others (pulmonary fibrosis with or without polymyositis, progressive encephalomyelitis, Mooren's corneal ulcers, erythema nodosum, chronic polyradiculonevritis) are mostly case reports. Howerver, even in cases of tight association, the mechanisms through which HCV may promote or induce extrahepatic manifestations remain unclear and merit further investigations.
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Affiliation(s)
- Damien Sène
- Department of Internal Medicine, Boulevard de l'hôpital, Paris, France
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Gad A, Tanaka E, Matsumoto A, el-Hamid Serwah A, Ali K, Makledy F, el-Gohary A, Orii K, Ijima A, Rokuhara A, Yoshizawa K, Nooman Z, Kiyosawa K. Factors predisposing to the occurrence of cryoglobulinemia in two cohorts of Egyptian and Japanese patients with chronic hepatitis C infection: ethnic and genotypic influence. J Med Virol 2003; 70:594-599. [PMID: 12794722 DOI: 10.1002/jmv.10435] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
The association between cryoglobulinemia and hepatitis C virus (HCV) infection has been reported. However, the factors underlying its wide variation of occurrence have not yet been well identified. To investigate this, cryoglobulinemia was studied in four cohorts of Egyptian and Japanese patients. Fifty Egyptian patients with chronic hepatitis C, infected with genotype 4 (the predominant HCV genotype in Egypt), were compared with 50 age- and sex-matched Japanese patients, infected with HCV genotype 1b (the predominant HCV genotype in Japan). Thirty-two Egyptian and 30 age- and sex-matched Japanese patients with chronic hepatitis B were included as controls. All patients were noncirrhotic. Antinuclear antibody (ANA), immunoglobulins (Ig), and cryoglubulins were assessed. Results showed a significantly higher prevalence of cryoglobulinemia in chronic hepatitis C Japanese genotype 1b (40%) as compared with Egyptian genotype 4 (14%), P = 0.003, while no difference was found between Japanese (17%) and Egyptian chronic hepatitis B controls (13%). Symptomatic cryoglobulinemia was more prevalent in the Japanese than in the Egyptian chronic hepatitis C group (10% vs. 4%), but the difference was not statistically significant. Univariate analysis showed no association between cryoglobulinemia and either age, sex, alanine aminotransferase level, or HCV viral load in Japanese or Egyptian patients, while the mean IgM level was significantly higher in the cryoglobulin-positive than in the cryoglobulin-negative chronic hepatitis C patients in each group (P = 0.003 and 0.017, respectively). Cryoglobulinemia was found to be significantly associated with both high IgG level (P = 0.020), and positive ANA (P < 0.001) in Japanese patients with chronic hepatitis C, genotype 1b but not in Egyptians with genotype 4. Multivariate analysis showed that the only factors predisposing to cryoglobulinemia were Japanese ethnicity with HCV genotype1b (P = 0.002, OR = 2.56), high IgM level of >245 mg/dl (P = 0.018, OR = 2.05) and female gender (P = 0.040, OR = 1/0.66). In conclusion, cryoglobulinemia is prevalent in Japanese patients with chronic hepatitis C infected with genotype 1b, but cryoglobulinemia is not common in Egyptians with HCV genotype 4. Although it was not possible to evaluate ethnicity and HCV genotype separately in this study, HCV genotype 1b appears to predispose more to cryoglobulinemia than does genotype 4. Female gender and high serum IgM level were also related.
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Affiliation(s)
- Amal Gad
- Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan
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