A hallmark of multiple sclerosis (MS) is intrathecal immunoglobulin (Ig) M synthesis (ITMS) due to the chronic activation of the immune system. Researchers discovered that ITMS is useful as a predictor of aggressive MS in patients with a clinically isolated syndrome (CIS), according to a study published in Neurology & Neuroinflammation.

In addition, researchers also compared the 4 different methods of assessing ITMS — IgM oligoclonal bands (OCMBs), Reibergram, lipid-specific OCMBs (LS-OCMBs), and IgM index — and discovered that LS-OCMBs is the best among them. 

ITMS has a mainly prognostic role and has been generally associated with the worse outcomes of MS. The purpose of this study was to assess the 4 methods of evaluating ITMS in patients with a CIS in terms of their capability to predict: 

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  • A second relapse
  • Reaching an irreversible Expanded Disability Status Scale (EDSS) score of 4 or 6
  • Conversion of the disease into secondary progressive MS (SPMS). 

Researchers conducted a single-center, observational study and recruited patients with a CIS at the Hospital Universitario Ramón y Cajal (HRC) referral MS center in Madrid, Spain. Patients included in the study had a follow-up of at least 2 years, as well as having CSF analysis performed, including intrathecal IgM and IgG synthesis. A total of 193 patients were included in the analysis; the median age was 31 and the median follow-up was 12.9 years. 

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The results show that the OCMB, LS-OCMB, and Reibergram methods of assessing ITMS significantly identified patients who were at risk of certain pre-existing outcomes, with LS-OCMB having the strongest associations. “LS-OCMB significantly identified patients with a CIS with a higher risk of a second relapse, reaching EDSS scores of 4 and 6 and converting to SPMS at an earlier stage in both unadjusted and multivariate analyses,” study authors stated.

This suggests that ITMS, particularly when assessed using LS-OCMB, can be an excellent biomarker in identifying patients who might be suitable candidates to receive early disease-modifying therapies (DMT). This is significant because the monoclonal antibodies used to treat MS are known to considerably improve prognosis when initiated at an early stage. 


Enric M, Susana SM, Lucienne C-F, et al. Predicting aggressive multiple sclerosis with intrathecal IgM synthesis among patients with a clinically isolated syndrome. Neurol Neuroimmunol Neuroinflamm. Published online July 22, 2021. doi:10.1212/NXI.0000000000001047