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

Background/Aim: Hepatitis C virus (HCV) infection is often associated with mixed cryoglobulins (MC) and may manifest as small-vessel vasculitis. It ha s been suggested that antibody (Ab) or sensitized T cells to HCV-containing endothelial cells may initiate the vasculitis process. Anti-endothelial ce ll antibodies (AECA) have been found in various connective tissue disorders , with a high prevalence in systemic vasculitis. The aim of the study was t o determine the prevalence of AECA in HCV patients with or without MC-assoc iated 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-associa ted vasculitis was noted in 25 patients who had at least one of the followi ng clinical features: peripheral neuropathy, glomerulonephritis, skin purpu ra, cerebral vasculitis. Group 2 included 20 patients with non-HCV viral di seases: HHV8 (10), miscellaneous (10). Group 3 included 25 patients with bi opsy-proven non-HCV chronic liver diseases: hepatitis B virus (10), miscell aneous (15). Controls were 100 blood donors (Group 4). Sera were adsorbed o nto a pellet of A549/8 epithelial cells before being evaluated. AECA were t hen 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 cryoglob ulin, antinuclear Ab, anticardiolipin Ab, and rheumatoid factor. Results: AECA were more frequently found in HCV patients than in blood dono rs (41% vs 5%,p=0.0001). The prevalence of AECA was lower in non-HCV than i n group 1 patients [group 2=15%, p=0.03; group 3= 16%, p=0.01]. There was n o significant difference in AECA prevalence between groups 2, 3 and 4. In H CV 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 Ib (p=0.005) and severity of liver histologic damage. AECA isotyp es were not different in the 4 groups. AECA were not associated with antinu clear Ab, anticardiolipin Ab, rheumatoid factor or interferon alpha treatme nt. Conclusion: AECA are a common finding in HCV patients (41%), but not in oth er viral diseases or in non-HCV chronic liver diseases. In HCV patients, AE CA are associated with MC-vasculitis, suggesting that AECA may be a marker for HCV-induced vasculitis.