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

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.

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.

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.

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.