Genetics

Intrathecal immunoglobulin G (IgG) synthesis is a defining biological feature of multiple sclerosis and a powerful predictor of disease course, yet its genetic basis has remained elusive. In this post, we explore a large multicenter genome-wide association study that uncovers a novel genetic locus in SAMD5, refines the role of the immunoglobulin heavy chain constant region, and clarifies how classical HLA risk alleles shape the CNS humoral immune response. By linking polygenic risk for MS to the presence and intensity of intrathecal IgG synthesis, the study provides new insight into how genetic susceptibility may influence disease severity through persistent antibody production within the central nervous system.