A New Serological Autoantibody Signature Associated with Multiple Sclerosis

The role of autoantibodies in the pathogenesis of Multiple Sclerosis (MS) remains incompletely understood. In this study, we analyzed serum samples from a cohort of MS patients in Qatar using high-throughput KoRectly Expressed (KREX) immunome protein-array technology. Compared to healthy controls, MS patients showed significantly altered autoantibody responses to 129 proteins, with a notable enrichment in autoantibodies targeting antiviral immune response-related proteins. Machine learning analysis identified a distinct molecular signature comprising 17 differentially expressed autoantibodies, including those against MX1, ISG20, MAX, SUFU, NR1H2, HMGN5, and EPHA10. Among these, autoantibodies against MX1-a key effector in the interferon-alpha/beta signaling pathway-showed the most pronounced increase, with nearly a threefold elevation in MS patients. While MX1 has previously been implicated in MS, this is the first report of autoantibody reactivity against the protein, suggesting a potential role in disease onset and progression. These findings support a link between antiviral immune responses and MS pathophysiology and offer a promising blood-based autoantibody signature that could inform future diagnostic and therapeutic strategies.