<p>Background and purpose: Patients with multiple sclerosis (MS) have altered T cell function and composition. Common genetic risk variants for MS affect proteins that function in the immune system. It is currently unclear to what extent T cell composition is affected by genetic risk factors for MS, and how this may precede a possible disease onset. Here, we aim to assess whether an MS polygenic risk score (PRS) is associated with an altered T cell composition in a large cohort of children from the general population. Methods: We included genotyped participants from the population-based Generation R study in whom immunophenotyping of blood T cells was performed at the age of 6 years. Analyses of variance were used to determine the impact of MS-PRSs on total T cell numbers (n = 1261), CD4<sup>+</sup> and CD8<sup>+</sup> lineages, and subsets therein (n= 675). In addition, T-cell-specific PRSs were constructed based on functional pathway data. Results: The MS-PRS negatively correlated with CD8<sup>+</sup> T cell frequencies (p = 2.92 × 10<sup>−3</sup>), which resulted in a positive association with CD4<sup>+</sup>/CD8<sup>+</sup> T cell ratios (p = 8.27 × 10<sup>−9</sup>). These associations were mainly driven by two of 195 genome-wide significant MS risk variants: the main genetic risk variant for MS, HLA-DRB1*15:01 and an HLA-B risk variant. We observed no significant associations for the T-cell-specific PRSs. Conclusions: Our results suggest that MS-associated genetic variants affect T cell composition during childhood in the general population.</p>

doi.org/10.1111/ene.15019, hdl.handle.net/1765/136900
European Journal of Neurology
Erasmus MC: University Medical Center Rotterdam

C.L. (Louk) de Mol, K.I.M. (Kirsten) Looman, M.M. (Marvin) van Luijn, K.L. (Karim) Kreft, P.R. (Philip) Jansen, MC van Zelm, … R.F. (Rinze) Neuteboom. (2021). T cell composition and polygenic multiple sclerosis risk. European Journal of Neurology, 28(11), 3731–3741. doi:10.1111/ene.15019