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Updated: Oct 27, 2025
Quantitative Measurement of Intrathecally Synthesized Proteins in Mice
Published on: November 29, 2019
Predicting Aggressive Multiple Sclerosis With Intrathecal IgM Synthesis Among Patients With a Clinically Isolated
Enric Monreal1, Susana Sainz de la Maza2, Lucienne Costa-Frossard2
1From the Department of Neurology (E.M., S.S.d.l.M., L.C.-F., J.C.Á.-C., J.M.), and Department of Immunology (P.W.-D., J.I.F.-V., N.V., M.E., P.L., I.T., L.M.V.), Hospital Universitario Ramón y Cajal, REEM, IRYCIS; Clinical Biostatistics Unit (J.Z.), Hospital Universitario Ramón y Cajal, IRYCIS, CIBERESP, Madrid, Spain; Institute of Metabolism and System Research (J.Z.), University of Birmingham, United Kingdom; and Department of Radiology (D.L.), Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain. enricmonreal@outlook.com.
Objective:
To determine the best method to measure intrathecal immunoglobulin (Ig) M synthesis (ITMS), a biomarker of worse prognosis in multiple sclerosis (MS). We compared the ability for predicting a poor evolution of 4 methods assessing ITMS (IgM oligoclonal bands [OCMBs], lipid-specific OCMBs [LS-OCMBs], Reibergram, and IgM index) in patients with a clinically isolated syndrome (CIS).
Methods:
Prospective study with consecutive patients performed at a referral MS center. We used unadjusted and multivariate Cox regressions for predicting a second relapse, Expanded Disability Status Scale (EDSS) scores of 4 and 6, and development of secondary progressive MS (SPMS).
Results:
A total of 193 patients were included, with a median (interquartile range) age of 31 (25-38) years and a median follow-up of 12.9 years. Among all methods, only OCMB, LS-OCMB, and Reibergram significantly identified patients at risk of some of the pre-established outcomes, being LS-OCMB the technique with the strongest associations. Adjusted hazard ratio (aHR) of LS-OCMB for predicting a second relapse was 2.50 (95% CI 1.72-3.64, p < 0.001). The risk of reaching EDSS scores of 4 and 6 and SPMS was significantly higher among patients with LS-OCMB (aHR 2.96, 95% CI 1.54-5.71, p = 0.001; aHR 4.96, 95% CI 2.22-11.07, p < 0.001; and aHR 2.31, 95% CI 1.08-4.93, p = 0.03, respectively).
Conclusions:
ITMS predicts an aggressive MS at disease onset, especially when detected as LS-OCMB.
Classification Of Evidence:
This study provides Class II evidence that lipid-specific IgM oligoclonal bands can predict progression from CIS to MS and a worse disease course over a follow-up of at least 2 years.
