IFN-α2 Autoantibody Screening and Functional Evaluation in Viral and Bacterial Infections

Abstract Background The presence of anti-interferon (IFN)-α2 autoantibodies is a strong indicator of severe disease course during viral infections and is observed in autoimmune diseases (e.g., myasthenia gravis). Detection of these autoantibodies during severe bacterial infections is understudied. Multiple anti-IFN-α2 autoantibody screening assays are available. However, the results do not always correlate with the neutralizing capacity of the autoantibodies. Methods Anti-IFN-α2 antibodies were measured by a Luminex-based assay in serum samples from individuals admitted to the intensive care unit infected with influenza (n = 38), invasive bacteria (n = 152), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 52). Anti-IFN-α2 antibodies were also studied in individuals with myasthenia gravis (n = 22) and in healthy individuals (n = 37). Individuals testing positive by Luminex were subsequently tested by enzyme-linked immunosorbent assay (ELISA) and tested for nonspecific reactivity and neutralization. Results Three of 16 Luminex-positive samples had nonspecific reactivity, 11/16 were positive by ELISA, and 10/16 had neutralizing activity. Anti-IFN-α2 antibodies were found in individuals infected with SARS-CoV-2 (7/52), influenza (3/38), invasive bacteria [2/152, of which 1 was Legionella pneumophilia and was 1 Escherichia coli (E. coli) (out of 39 E. coli infections)], and in individuals with myasthenia gravis (2/22). Conclusions Anti-IFN-α2 autoantibodies were detected in viral infections, myasthenia gravis, and rarely in bacterial infections. ELISA and Luminex screening assays do not give similar results. Nonspecific reactivity and functional assays are necessary to validate the screening test result.