SHARJAH — Researchers from the University of Sharjah and an international consortium published a study in the journal Cell, revealing that pre-existing autoimmune B-cell responses targeting type I interferons underlie severe viral infections like COVID-19. The study, titled Affinity-matured B cell responses neutralizing type-I interferons underlie severe viral infections by M. Fournier et al., examines type I interferons, a group of signaling proteins that form one of the body's first lines of defense against viral infections.

The study found that type I interferons were unable to effectively combat the coronavirus in some patients because they harbored a large and diverse population of B cells that target the interferons themselves. The abnormal immune response was detectable in patients before they developed life-threatening viral disease.

The study involved scientists from universities and research institutions in France, Switzerland, Canada, Spain, Belgium, Saudi Arabia, Sweden, Denmark, Italy, the U.S., Estonia, and the United Arab Emirates. The researchers combined X-ray crystallography with AlphaFold3-based structural analyses to examine hundreds of patient-derived monoclonal antibodies. The analysis revealed that the antibodies target three major B-cell epitopes covering all principal regions of type I interferons.

Rabih Halwani, Professor of Immunology, said, "We showed that these B cells had undergone a prolonged process called affinity maturation." He added, "Under normal circumstances, affinity maturation improves the ability of antibodies so that they bind more strongly to invading microbes." He said, "In this case, however, the same process strengthened antibodies directed against the body's own interferons." He stated, "They identified three major regions, or epitopes, on the interferon molecules that were repeatedly targeted." He added, "Collectively, these antibodies were capable of recognizing and neutralizing different type I interferons, including interferon-α and interferon-ω." He added, "Overall, these findings change the way we should view these autoantibodies." He said, "They are not merely accidental antibodies that appear during a serious infection." He stated, "Instead, they arise from an organized, mature, and persistent autoimmune B-cell response that may exist silently before they become infected." The study noted, "These findings support a model in which a germinal-center-derived memory B-cell response directed against type I IFNs is established before severe viral infection, providing a core mechanism linking T-cell tolerance defect to pathogenic AAN-I-IFNs underlying severe viral diseases." The study has the DOI 10.1016/j.cell.2026.04.013.