Cellular origin and characterization of autoantibodies against type I IFNs in COVID-19 and APS-1.

A subgroup of severe COVID-19 patients shows strong binding to multiple type I IFNs, and integrated single-cell BCR profiling links this to IFN-β2-binding and -neutralizing antibody–enriched B cell states.

• Why it matters: Type I IFN autoantibodies can undermine antiviral defense, but how they arise and which B cell compartments generate functional neutralizers is unclear.
• What they did: The team used high-throughput autoantigen profiling plus integrated single-cell RNA and BCR sequencing with functional assays, then compared findings with APS-1 patients.
• The result: Competition surface plasmon resonance and AlphaFold 3 modeling defined three epitope groups and seven structural subclasses, and functional IFN-neutralizing antibodies were mainly in memory and atypical B cells.

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