Systemic Autoimmune Diseases in Patients with Hepatitis C Virus Infection: Characterization of 1020 Cases (The HISPAMEC Registry)

Laboratory of Autoimmune Diseases Josep Font, Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, 08036-Barcelona, Spain.
The Journal of Rheumatology (Impact Factor: 3.19). 05/2009; 36(7):1442-8. DOI: 10.3899/jrheum.080874
Source: PubMed


To describe the clinical and immunologic characteristics of a large series of patients with systemic autoimmune diseases (SAD) associated with chronic hepatitis C virus (HCV) infection.
The HISPAMEC Registry is a multicenter international study group dedicated to collecting data on patients diagnosed with SAD with serological evidence of chronic HCV infection. The information sources are cases reported by physicians of the HISPAMEC Study Group and periodic surveillance of reported cases by a Medline search updated up to December 31, 2007.
One thousand twenty HCV patients with SAD were included in the registry. Patients were reported from Southern Europe (60%), North America (15%), Asia (14%), Northern Europe (9%), South America (1%), and Australia (1%). Countries reporting the most cases were Spain (236 cases), France (222 cases), Italy (144 cases), USA (120 cases), and Japan (95 cases). The most frequently reported SAD were Sjögren's syndrome (SS; 483 cases), rheumatoid arthritis (RA; 150 cases), systemic lupus erythematosus (SLE; 129 cases), polyarteritis nodosa (78 cases), antiphospholipid syndrome (59 cases), inflammatory myopathies (39 cases), and sarcoidosis (28 cases). Twenty patients had 2 or more SAD. Epidemiological data were available in 677 cases. Four hundred eighty-seven (72%) patients were female and 186 (28%) male, with a mean age of 49.5 +/- 1.0 years at SAD diagnosis and 50.5 +/- 1.1 years at diagnosis of HCV infection. The main immunologic features were antinuclear antibody (ANA) in 61% of patients, rheumatoid factor (RF) in 57%, hypocomplementemia in 52%, and cryoglobulins in 52%. The main differential aspect between primary and HCV-related SAD was the predominance of cryoglobulinemic-related markers (cryoglobulins, RF, hypocomplementemia) over specific SAD-related markers (anti-ENA antibodies, anti-dsDNA, anti-cyclic citrullinated peptide) in patients with HCV.
In the selected cohort, the SAD most commonly reported in association with chronic HCV infection were SS (nearly half the cases), RA and SLE. Nearly two thirds of SAD-HCV cases were reported from the Mediterranean area. In these patients, ANA, RF and cryoglobulins are the predominant immunological features.

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    • "The features that mainly mark VH1-69 autoreactivity profile are basically its framework amino acid sequences and the abnormal CDR3 length. These characteristics are mainly responsible for the binding to hydrophobic pockets on the viral envelope and therefore for VH1-69-related neutralizing activity but, on the other side, are burdened by the potential cross-recognition of self-antigens (host cell membranes) leading to autoreactivity phenomena [46] (Table 1). A practical example of infection-related autoimmune diseases is type II mixed cryoglobulinemia (MCII), a clinical syndrome of systemic inflammation characterized by systemic vasculitis caused by the deposition of immune complexes on small vessel walls [47]. "
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    ABSTRACT: It is known that even the adaptive components of the immune system are based on genetic traits common to all individuals, and that diversity is shaped by the lifelong contacts with different non-self antigens, including those found on infectious pathogens. Besides the individual differences, some of these common traits may be more prone to react against a given antigen, and this may be exploited by the infectious pathogens. Indeed, viral infections can deregulate immune response by subverting antibody (Ab) gene usage, leading to the overexpression of specific Ab subfamilies. This overexpression often results in a protective antiviral response but, in some cases, also correlates with a higher likelihood of developing humoral autoimmune disorders. These aspects of virus-induced autoimmunity have never been thoroughly reviewed, and this is the main purpose of this review. An accurate examination of virus specific Ab subfamilies elicited during infections may help further characterize the complex interplay between viruses and the humoral immune response, and be useful in the design of future monoclonal antibody (mAb)-based anti-infective prophylactic and therapeutic strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Seminars in Immunology 04/2015; 27(2). DOI:10.1016/j.smim.2015.03.008 · 5.17 Impact Factor
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    • "With regard to other possible HCV-associated disorders, namely Beçhet's syndrome, systemic lupus erythematosus, and antiphospholipid syndrome, data reported in the literature are generally anecdotal [8,9,29,48,49]. Even if a possible causative role of HCV in these autoimmune diseases cannot be totally excluded, these patients might be better classified as having a simple comorbidity. "
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    Arthritis research & therapy 06/2012; 14(3):215. DOI:10.1186/ar3865 · 3.75 Impact Factor
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    • "Hepatitis C virus (HCV) is commonly associated with autoimmune diseases as extrahepatic manifestations (EHM) [1] The most important autoimmune diseases associated with HCV are mixed essential cryoglobulinemia (MEC) [2] and Sjögren syndrome (SS) [3]. Other autoimmune diseases have been described in patients with HCV, but the association has not been well documented. "
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    ABSTRACT: Extrahepatic immunological manifestations of hepatitis C virus (HCV) are well described. In addition, antiglutamic acid decarboxylase (GAD) antibody-associated cerebellar ataxia is well-established entity. However, there have been no reports in the literature of anti-GAD antibody-associated ataxia as an extrahepatic manifestation of HCV infection. We report the case of a young woman with chronic hepatitis C virus and multiple extrahepatic autoimmune diseases including Sjögren syndrome and pernicious anemia who presented with subacute midline cerebellar syndrome and was found to have positive antiglutamic acid decarboxylase (GAD) antibody in the serum and cerebrospinal fluid. An extensive diagnostic workup to rule out neoplastic growths was negative, suggesting the diagnosis of nonparaneoplastic antiglutamic acid decarboxylase antibody-associated cerebellar ataxia as an additional extrahepatic manifestation of hepatitis C virus infection. The patient failed to respond to high-dose steroids and intravenous immunoglobulin. Treatment with the monoclonal antibody rituximab stabilized the disease. We postulate that anti-GAD associated ataxia could be an extrahepatic manifestation of HCV infection.
    07/2011; 2011:975152. DOI:10.1155/2011/975152
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