A new serological autoantibody signature associated with multiple sclerosis.

Abstract

The role of autoantibodies in the pathogenesis of Multiple Sclerosis (MS) remains incompletely understood. In this study, we analysed 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 and oligodendrocyte marker SOX-10. 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 signalling 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.