Predicting Aggressive Multiple Sclerosis With Intrathecal IgM Synthesis Among Patients With a Clinically Isolated Syndrome

• Published in: Neurology : neuroimmunology & neuroinflammation Vol. 8; no. 5
• Main Authors: Monreal, Enric, Sainz de la Maza, Susana, Costa-Frossard, Lucienne, Walo-Delgado, Paulette, Zamora, Javier, Fernández-Velasco, José Ignacio, Villarrubia, Noelia, Espiño, Mercedes, Lourido, Daniel, Lapuente, Paloma, Toboso, Inmaculada, Álvarez-Cermeño, José Carlos, Masjuan, Jaime, Villar, Luisa María
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins 01.09.2021
• Subjects: Adult; Biomarkers - blood; Biomarkers - cerebrospinal fluid; Female; Humans; Immunoglobulin M - blood; Immunoglobulin M - cerebrospinal fluid; Male; Multiple Sclerosis - blood; Multiple Sclerosis - cerebrospinal fluid; Multiple Sclerosis - diagnosis; Multiple Sclerosis - immunology; Oligoclonal Bands - blood; Oligoclonal Bands - cerebrospinal fluid; Prospective Studies; Sensitivity and Specificity
• ISSN: 2332-7812; 2332-7812
• DOI: 10.1212/NXI.0000000000001047

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). 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). 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, < 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, = 0.001; aHR 4.96, 95% CI 2.22-11.07, < 0.001; and aHR 2.31, 95% CI 1.08-4.93, = 0.03, respectively). ITMS predicts an aggressive MS at disease onset, especially when detected as LS-OCMB. 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.