Prevalence of hepatitis C serum antibody in autoimmune diseases

Abstract

Objective

To evaluate the prevalence of serum antibodies against hepatitis C virus and other infectious agents in a large cohort of well-characterized patients with autoimmune diseases (AID).

Methods

We utilized 1322 sera from patients with 18 different AID and 236 sera from healthy controls from the same countries and with similar age and sex distribution. All sera were tested for the presence of serum anti-hepatitis C virus (HCV) antibodies as well as antibodies directed at other infectious agents and autoantibodies.

Results

Anti-HCV antibody was detected in 115/1322 (8.7%) of patients with AID and 0.4% of matched healthy controls (P < 0.0001). The prevalence of anti-HCV antibody was significantly higher in 7/18 different AID (i.e. cryoglobulinemia, mixed cryoglobulinemia pemphigus vulgaris, vasculitis, secondary anti-phospholipid syndrome, Hashimoto's thyroiditis, and inflammatory bowel disease) compared to controls. Patients with AID and serum anti-HCV positivity had an increased prevalence of antibodies against hepatitis B virus, Toxoplasma gondii and Cytomegalovirus as opposed to a lower frequency of serum autoantibodies.

Conclusions

The enhanced prevalence of anti-HCV serum antibodies in AID may suggest a role for HCV in tolerance to breakdown, similarly to its established role in mixed cryoglobulinemia. This immune mediated effect does not rule out the role of other infectious agents.

Introduction

The link between infectious diseases and autoimmune diseases (AID) has been repeatedly suggested based mostly on epidemiological and experimental data [1], [2], [3], [4]. Various infectious agents are known to trigger tolerance breakdown, as in the case of hepatitis C virus (HCV) in specific conditions [2], [5]. Chronic liver disease associated with HCV affects 70–90% of infected subjects [6] and is frequently associated with extra hepatic manifestations [7]. The worldwide prevalence of HCV chronic infection is estimated to range between 2 and 3% of the general population [8], [9]. Indeed, extra hepatic manifestations of chronic HCV-infection [10] include autoimmune phenomena [11] and hematopoietic malignancy [12]. Among the former, it is not uncommon to detect serum anti-nuclear antibodies (ANA), cryoglobulins, rheumatoid factor (RF), anti-smooth muscle antibodies (SMA), anti-cardiolipin (aCL), anti-liver kidney microsomal 1 (LKM1), and anti-thyroid antibodies [13], [14], [15], [16], [17], [18], [19], along with overt autoimmunity (as in the case of cryoglobulinemia) or variants of AID (i.e. Sjögren-like syndrome) [13], [15], [20], [21].

The mechanisms linking HCV with autoimmunity are unclear. HCV targets hepatocytes but can also replicate in other cells, such as lymphocytes [14] particularly B-cells [7], [8], [22]. Studies from our group [19] and others [23], [24], [25] demonstrated an increased level of B-lymphocyte activating factor (BAFF), a B-cell's survival factor, in chronic HCV-infection and suggest that B-cells activation and increased survival might play a role in HCV-associated autoimmunity. Other proposed mechanisms include the potential of HCV to induce auto-reactive CD8+T cells by molecular mimicry [26], the induction of high levels of endogenous IFNα [27], direct viral invasion and bystander activation [14], [28], [29].

Several authors have evaluated the prevalence of AID in HCV-infection using case-control studies, with conflicting results [11], [21], [27], [28], [30], [31], [32], [33]. We herein report a complementary approach that investigated a large series of patients with defined AID for the prevalence of anti-HCV-antibodies as well as antibodies directed at other infectious agents and autoantigens. Our data support a significantly higher prevalence of serum anti-HCV antibody in patients with autoimmune diseases compared to healthy controls.