Multiplex Detection of Immunoglobulins Uncovers Intrathecal IgA Elevation in Multiple Sclerosis

Background: Intrathecal IgG synthesis is a well-established hallmark of multiple sclerosis (MS), yet the roles of other immunoglobulin isotypes remain under investigated. This study aimed to comprehensively profile immunoglobulin distributions in cerebrospinal fluid (CSF) and plasma from MS patients and neurological controls. Methods: Paired CSF and plasma samples from 23 MS patients and 20 neurological controls were analyzed using a multiplex Luminex-based immunoassay targeting IgG1-4, IgA, and IgM. The findings were validated using commercial ELISA kits and Western blot analysis. Results: Multiplex analysis revealed a selective intrathecal enrichment of IgA and IgM in MS CSF, with significantly higher levels compared to both matched plasma and control CSF. IgG1 was modestly elevated in MS CSF by ELISA but not by multiplex assay. Western blotting confirmed a robust elevation of IgA in MS CSF, providing qualitative support for intrathecal enrichment rather than definitive proof of synthesis. Conclusions: These findings uncover previously underappreciated selective enrichment of IgA and IgM in the MS CNS compartment, complementing, rather than replacing, the established IgG-centric paradigm. The results suggest alternative antibody-mediated mechanisms in MS and highlight the importance of assay selection in biomarker discovery, which suggests IgA as an emerging component of MS immunopathology.