Anti-endothelial cell auto-antibodies in hepatitis C virus mixed cryoglobulinemia

Abstract

Background/aim: Hepatitis C virus (HCV) infection is often associated with mixed cryoglobulins (MC) and may manifest as small-vessel vasculitis. It has been suggested that antibody (Ab) or sensitized T cells to HCV-containing endothelial cells may initiate the vasculitis process. Anti-endothelial cell antibodies (AECA) have been found in various connective tissue disorders, with a high prevalence in systemic vasculitis. The aim of the study was to determine the prevalence of AECA in HCV patients with or without MC-associated vasculitis, and to identify associations with clinical, immunological, virological and liver characteristics.

Methods: Sixty-nine HCV patients (Group 1), 46 of whom had MC (type II=30, type III=16), and 23 without MC, were prospectively studied. HCV-MC-associated vasculitis was noted in 25 patients who had at least one of the following clinical features: peripheral neuropathy, glomerulonephritis, skin purpura, cerebral vasculitis. Group 2 included 20 patients with non-HCV viral diseases: HHV8 (10), miscellaneous (10). Group 3 included 25 patients with biopsy-proven non-HCV chronic liver diseases: hepatitis B virus (10), miscellaneous (15). Controls were 100 blood donors (Group 4). Sera were adsorbed onto a pellet of A549/8 epithelial cells before being evaluated. AECA were then searched using a cellular ELISA, with a permanent cell line (EA.hy 926) as the substrate. All sera were also examined for the presence of cryoglobulin, antinuclear Ab, anticardiolipin Ab, and rheumatoid factor.

Results: AECA were more frequently found in HCV patients than in blood donors (41% vs 5%, p=0.0001). The prevalence of AECA was lower in non-HCV than in group 1 patients [group 2=15%, p=0.03; group 3=16%, p=0.01]. There was no significant difference in AECA prevalence between groups 2, 3 and 4. In HCV patients, AECA were associated with age (p<0.001), the presence of MC (p=0.008), cryoglobulin level (p=0.016), HCV-associated vasculitis (p=0.04), genotype 1b (p=0.005) and severity of liver histologic damage. AECA isotypes were not different in the 4 groups. AECA were not associated with antinuclear Ab, anticardiolipin Ab, rheumatoid factor or interferon alpha treatment.

Conclusion: AECA are a common finding in HCV patients (41%), but not in other viral diseases or in non-HCV chronic liver diseases. In HCV patients, AECA are associated with MC-vasculitis, suggesting that AECA may be a marker for HCV-induced vasculitis.