Prognostic role of intrathecal IgM synthesis in multiple sclerosis: Results from a clinical series
Mattia Fonderico, Tiziana Biagioli, Luisa Lanzilao, Angelo Bellinvia, Roberto Fratangelo, Luisa Pastò, Elio Prestipino, Lorenzo Razzolini, Laura Tudisco, Andrea Ginestroni, Luisa Vuolo, Enrico Fainardi, Clara Ballerini, Emilio Portaccio, Maria Pia Amato
Abstract
Background: There is emerging evidence that intrathecal IgM synthesis (ITMS) is a risk factor for conversion to clinically defined multiple sclerosis (CDMS) in clinically isolated syndrome (CIS) patients. Objectives: The objective of this study is to verify the prognostic role of ITMS as a risk factor for the second clinical attack in patients after the first demyelinating event. Methods: Monocentric observational study performed on prospectively acquired clinical data and retrospective evaluation of magnetic resonance imaging (MRI) data. ITMS was assessed according to Reiber’s non-linear function. We compared time to the second attack by using Kaplan–Meier curves and performed adjustment by Cox regression analysis. Results: Demographics and clinical data were collected prospectively in a cohort of 68 patients. ITMS occurred in 40% (27/68) of patients who had a higher T1-hypointense lesion load at brain MRI ( p = 0.041). In multivariate Cox regression analysis (adjusted for age, sex, baseline Expanded Disability Status Scale, IgG oligoclonal bands and disease-modifying treatment exposure), relapsing-remitting multiple sclerosis (MS) patients with ITMS were at higher risk to experience a second clinical attack (adjusted hazard ratio (aHR) = 6.3, 95% confidence interval (CI) = 2.1–18.4, p = 0.001). Conclusion: Together with previous studies, our findings support the role of ITMS as a prognostic biomarker in MS.