Multiple sclerosis (MS) is a devastating inflammatory disease of the central nervous system, of which the cause is still unclear and the clinical course is highly unpredictable. There is one environmental factor that connects all patients with MS: the Epstein-Barr virus (EBV). The chance of developing MS is 32 times higher after an EBV infection. Moreover, variation within the human leukocyte antigen (HLA) system contributes by far the most to the genetic risk of MS. Previously, Marvin and his team identified distinct B- and T-cell subsets with enhanced capacity to infiltrate the MS brain. Given the association of these subsets with EBV, in-depth insight into how protective and risk HLA alleles define their functional interplay and response to EBV will bring us closer to the roots of MS.
The main goal of his fellowship is to expose the functional ‘Lymphocytes and IgGs with risk HLA-resTricted EBV Reactivity’ (‘LIGHTER’) of MS. In this project, a cohort of early MS patients (part of MS center ErasMS; www.erasms.nl) will be stratified based on the distribution of protective and risk HLA alleles. The obtained HLA genetic risk burden shall be correlated with disease activity, EBV load and anti-EBV Ig titers. Patients with a high and low risk burden will be compared for B- and T-cell effector programs using state-of-the-art technology, including single-cell RNA-seq and 38 color-based spectral cytometry. The ‘LIGHTER’ of MS will be further uncovered through in vitro B- and T-cell differentiation assays and peptide stimulations and the use of both B- and T-cell tetramers.
The MS-fellowship is a personal grant with the purpose to retain excellent researchers within the local MS community. This research project is made possible by contributors of Stichting MS Research, including all participants of TheMay50K.
For more information about this study (in Dutch), please see: