Intrathecal Immunoglobulin M Synthesis Predicts Disease Activity and Severity in Multiple Sclerosis

Researchers have identified that intrathecal synthesis of immunoglobulin M (IgM) is a stronger biomarker for disease activity and severity when compared to oligoclonal immunoglobulin G (IgG) bands and intrathecal synthesis of immunoglobulin G, according to a recent study published in Annals of Neurology.

“The clinical course of multiple sclerosis is heterogenous and unpredictable on individual

grounds at the time of diagnosis. Biomarkers bridging this prognostic gap are urgently

needed for personalized therapeutic decision making,” wrote Johanna Oechtering, MD, Neurology Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB) University Hospital Basel, University of Basel, Switzerland, and co-researchers.

Combined categorical analyses and qualitative analyses were applied to determine if intrathecal synthesis of IgM and IgG (IgMIF and IgGIF) in patients with relapsing MS are associated with outcomes including inflammatory activity or an increase in disease severity.

Researchers observed 530 patients with relapsing MS at baseline and follow-up for cerebrospinal fluid, data from magnetic resonance imaging scans in addition to clinical data, and serum neurofilament light chain (sNfL) levels.

Patients were categorized by presence of oligoclonal IgG bands or IgMIF and IgGIF .

Covariate adjusted statistical models looked into relapse rate, sNfL levels, T2-weighted lesions, multiple sclerosis severity score, and initiation time of high efficacy therapy in participating patients with relapsing MS.

Categorical analysis showed that patients with IgMIF had a significantly shorter time to first relapse, 28 months shorter, shorter time to initiation of high efficacy therapy, and had a higher average multiple sclerosis severity score than those without intrathecal IgM synthesis.

Patients with IgMIF also had higher sNfL levels, more new/enlarging T2w lesions, and higher total lesion counts.

“This large study supports the value of intrathecal IgM synthesis as an independent biomarker of disease activity and severity in relapsing MS,” concluded Dr Oechtering, et al. —Erin McGuinness

Oechtering J, Schaedelin S, Benkert P, et al. Intrathecal Immunoglobulin M synthesis is an independent biomarker for higher disease activity and severity in multiple sclerosis [published online ahead of print, 2021 May 31]. Ann Neurol. 2021;10.1002/ana.26137. doi:10.1002/ana.26137