Anti-Soluble Liver Antigen (SLA) Antibodies in Chronic HCV Infection

Abstract

Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble liver antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP^(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble liver antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the liver injury of patients chronically infected by HCV needs further investigation.

• Hepatitis C virus
• Autoimmune hepatitis
• Soluble liver antigen (SLA)
• Autoantibodies
• aa, amino acid
• AIH, autoimmune hepatitis
• bp, base pair
• ELISA, enzyme-linked immuno-assay
• FTCD, formiminotransferase cyclodeaminase
• HCV, hepatitis C virus
• IgG, immunoglobulin G
• IPA, immunoprecipitation assay
• LC1, liver cytosol type 1
• LKM1, liver kidney microsome type 1
• PCR, polymerase chain reaction
• SDS/PAGE, sodium dodecyl sulphate-polyacrylamide gel
• SLA, soluble liver antigen
• WB, western blot