Reduced CD40 expression in B cell subsets of individuals with radiologically isolated syndrome
Year: 2025
Type: article
Study design: Observational Study
Abstract: Introduction: B cells play a central role in multiple sclerosis (MS) pathogenesis, yet their activation profiles during the earliest disease stages remain incompletely characterized. We aimed to investigate the expression of the activation markers CD40 and CD71 across peripheral B cell subsets in individuals with radiologically isolated syndrome (RIS), and compare them to those with clinically isolated syndrome or MS (CIS/MS) and healthy controls (HC). Methods: Peripheral blood cells from individuals with RIS (n=21), CIS/MS (n=15), and HC (n=15) were analyzed by flow cytometry. CD40 and CD71 expression was assessed across major B cell subsets. Epstein-Barr virus (EBV) serologies were measured to explore associations with activation marker expression. Results: CD40 expression was reduced on transitional, naïve, B cell subsets in RIS compared to CIS/MS and HC (p<0.001). CD71 expression remained stable across groups. CD40 expression was preserved in plasmablasts and regulatory B cells. No significant associations were observed between CD40 levels and EBV antibody titers. Discussion: In this cross-sectional cohort, CD40 expression was lower on transitional, naïve, and memory B cell subsets in RIS compared to CIS/MS and HC, whereas plasmablasts and regulatory B cells were comparable. This pattern is consistent with an altered costimulatory state in early, asymptomatic disease and warrants longitudinal studies to determine its clinical relevance.
Source: Frontiers in Immunology
Authors: Christian W. Keller, Kerstin Stein, Andreu Vilaseca, Luisa M. Villar, Gary Álvarez-Bravo, Maria Protopapa, Josef Shin, Nicolás Fissolo, José Enrique Martínez-Rodríguez, Ana Quiroga-Varela, Alexis García-Sarreón, Lucía Gutiérrez, Luciana Midaglia, Xavier Montalban, Jan D. Lünemann, Manuel Comabella
Institutions: University of Freiburg, University of Münster, University Medical Center Freiburg, University Hospital Münster, Universitat Autònoma de Barcelona, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Centre d'Esclerosi Múltiple de Catalunya, Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón y Cajal, Universitat de Girona, Instituto de Salud Carlos III, Institut d'Investigació Biomèdica de Girona, Hospital Santa Caterina, Hospital Universitari de Girona Doctor Josep Trueta, Johannes Gutenberg University Mainz, University Medical Center of the Johannes Gutenberg University Mainz, Biomedical Research Networking Center on Neurodegenerative Diseases, Hospital Del Mar, Municipal Institute for Medical Research, Hospital del Mar Research Institute
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
Funder: Instituto de Salud Carlos III
OpenAlex ID: W4416839064