Immunoglobulin M Oligoclonal Bands: Biomarker of Targetable Inflammation in Primary Progressive Multiple Sclerosis

Objective: To identify a biomarker distinguishing patients who, despite a primary progressive multiple sclerosis (PPMS) clinical course, may nonetheless benefit from immune therapy. Methods: The presence or absence of both immunoglobulin (Ig) G and IgM oligoclonal bands (OCB) was blindly examined in paired cerebrospinal fluid (CSF) and serum samples from a large PPMS patient cohort, and related to clinical and imaging evidence of focal inflammatory disease activity. Results: Using both cross-sectional samples and serial sampling in a subgroup of patients followed prospectively as part of the placebo-controlled OLYMPUS study of rituximab in PPMS, we found that the presence of CSF-restricted IgM OCB (but not of IgG OCB) is associated with an active inflammatory disease phenotype in PPMS patients. This finding was confirmed in an independent, multicenter validation cohort. Interpretation: The presence of CSF IgM OCB may be a biomarker for a subset of PPMS patients with more active inflammatory disease, who may benefit from immune-directed treatments.