Soluble HLA class I antigens in chronic hepatitis C: a disease-associated manifestation or molecules modulating...

The occurrence of high levels of soluble human leukocyte class I antigens (sHLA-I) represents an usual finding during the course of different clinical conditions, such as viral infections and autoimmune disorders. On the other hand, the well known property of sHLA-I to modulate T cell responsiveness could be taken as an advantage to improve long-term allograft acceptance. Recent data have pointed out that subjects with chronic hepatitis C virus (HCV) infection exhibit high amounts of sHLA-I, a pattern which has also been used for monitoring host responsiveness to interferon alpha (IFN-alpha) therapy. However, the lack of correlation between lymphocyte infiltration at liver site and disease biological activity suggests a potential role for sHLA-I in T cell dysfunction during chronic hepatitis C. sHLA-I antigens may, in fact, either interact with T cell receptor delivering an inhibitory signal or trigger cytotoxic T lymphocyte apoptosis by inducing CD95 ligand expression. Both events seem to favour HCV replication and liver tissue damage progression. Alltogether, these findings indicate that, besides viral variant generation and HCV core-mediated immunosuppression, sHLA-I may contribute to the imbalance of immunoresponsiveness during chronic HCV infection.