Immunoglobulin M oligoclonal bands: biomarker of targetable inflammation in primary progressive multiple sclerosis

Ann Neurol. 2014 Aug;76(2):231-40. doi: 10.1002/ana.24190. Epub 2014 Jul 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / cerebrospinal fluid
  • Cross-Sectional Studies
  • Female
  • Humans
  • Immunoglobulin M / cerebrospinal fluid*
  • Inflammation / cerebrospinal fluid
  • Inflammation / immunology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / cerebrospinal fluid
  • Multiple Sclerosis, Chronic Progressive / immunology*
  • Oligoclonal Bands / cerebrospinal fluid*
  • Phenotype


  • Biomarkers
  • Immunoglobulin M
  • Oligoclonal Bands