Neutralizing antibodies to interferon alfa arising during peginterferon therapy of chronic hepatitis B in children and adults: Results from the HBRN trials
Muhammad Atif Zahoor, Joshua B. Feld, Hsing-Hua Sylvia Lin, Alexander I. Mosa, Loghman Salimzadeh, Robert P. Perrillo, Raymond T. Chung, Kathleen B. Schwarz, Harry LA Janssen, Adam J. Gehring, Jordan J. Feld- Hepatology
Background:
Peginterferon-α (PegIFNα) is of limited utility during immunotolerant (IT) or immune active (IA) phases of chronic hepatitis B infection but is being explored as part of new cure regimens. Low/absent levels of IFNα found in some treated patients are associated with limited/no virological responses.
Aim:
To determine if sera from participants inhibit IFNα activity and/or contain therapy-induced anti-IFNα antibodies.
Methods:
Pre-, on- and post-treatment sera from 61 IT trial participants on PegIFNα/ entecavir therapy and 88 IA trial participants on PegIFNα/tenofovir therapy were screened for anti-IFNα antibodies by indirect ELISA. The neutralization capacity of antibodies was measured by pre-incubation of sera +/- recombinant-human IFNα (rhIFNα) added to Huh7 cells with measurement of interferon stimulated gene (ISG)-induction by qPCR. Correlations between serum-induced ISG inhibition, presence, and titer of anti-IFNα antibodies and virological responses were evaluated.
Results:
Pre-incubation of on-treatment serum from 26 IT (43%) and 13 IA (15%) participants with rhIFNα markedly blunted ISG-induction in Huh7 cells. Degree of ISG-inhibition correlated with IFNα antibody titer (
Conclusions:
The development of anti-IFNα nAbs during PegIFNα treatment diminishes responses to antiviral therapy. Understanding how and why anti-IFNα antibodies develop may allow for optimization of IFN-based therapy, which is critical given its renewed use in HBV-cure strategies.