Mitigating adverse effects of B cell depletion therapy on acute respiratory virus infections through IFN-β intervention treatment.

Abstract

Abstract In autoimmune patients, the use of disease-modifying therapies (DMTs) can compromise immunity to viral infections. The COVID-19 pandemic generated interest in the effects of two DMTs on acute viral infections:B cell depletion therapy (α-CD20) and Interferon-beta (IFN-β) therapy. Severe acute viral infections have been associated with B cell depletion therapy, while IFN-β is believed to provide protection due to its antiviral properties. The goal of our study is to elucidate the individual and combined effects of α-CD20 and IFN-β during acute respiratory viral infections in mice. In our study, B cell depletion was achieved by administering α-CD20 three times every 5 days, starting 7 days before influenza A virus (IAV) infection, while IFN-β was given on days 1 and 2 post-infection. When administered alone, α-CD20 resulted in increased weight loss, reduced viral clearance, heightened lung-infiltrating myeloid cells, and elevated inflammatory cytokines in the blood on day 9 post-infection. T cell responses to IAV were not inhibited by α-CD20. While IFN-β alone did not protect against IAV, co-administration of IFN-β with α-CD20 effectively mitigated adverse effects of B cell depletion, by reducing viral load, mitigating morbidity, and slowing the infiltration of myeloid cells into the lung. These data demonstrate IFN-β’s ability to counteract α-CD20’s negative impact on viral infections, providing insights for potential treatment strategies in autoimmunity during viral outbreaks.