Therapy-Induced Antibodies Against the Antiviral and Antiproliferative Effects of Interferons in Patients with Chronic Hepatitis C Virus Infection

Sera from 86 patients with chronic hepatitis C virus (HCV) infection treated with recombinant interferons-α (rIFN-α) were screened for IFN-binding and antiviral effect-neutralizing antibodies. Out of the 61 patients treated with rIFN-α2b, 46% had binding and 28% had neutralizing antibodies. 44% of the 25 patients treated with rIFN-α2a developed binding antibodies and 24% had neutralizing antibodies. Contradictory data were observed concerning the appearance of anti-IFN antibodies and the outcome of IFN therapy. A significantly higher number of the patients with a sustained response to rIFN-α2b therapy formed antibodies than the number among the non-responder patients. At the same time, in the patients treated with rIFN-a2a, opposite data were found. The activity of the antibodies in some sera was studied against the antiproliferative effect of IFNs on Daudi cells by measuring the [3H]thymidine incorporation. The binding antibodies without neutralization of the antiviral effect of the IFNs inhibited the antiproliferative activity of the rIFNs, similarly to antibodies having both IFN-binding and antiviral effect-neutralizing capacities. At the same time, the antiproliferative effect of the natural IFN was less affected. It is suggested that the antiproliferative assay is more sensitive than the antiviral method for demonstration of the presence of antibodies exerting an inhibitory effect on the biological activities of IFN