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. 2024 Sep:148:103279.
doi: 10.1016/j.jaut.2024.103279. Epub 2024 Jul 6.

Impact of coding risk variant IFNGR2 on the B cell-intrinsic IFN-γ signaling pathway in multiple sclerosis

Laurens Bogers  1 , Jasper Rip  1 , Liza Rijvers  1 , Jamie van Langelaar  1 , Steven C Koetzier  1 , Kirsten L Kuiper  1 , Veronique Meerdink  1 , Annet F Wierenga-Wolf  1 , Marie-José Melief  1 , Ana M Marques  1 , Joost Smolders  2 , Marvin M van Luijn  3
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Free article

Impact of coding risk variant IFNGR2 on the B cell-intrinsic IFN-γ signaling pathway in multiple sclerosis

Laurens Bogers et al. J Autoimmun. 2024 Sep.
Free article

Abstract

B cells of people with multiple sclerosis (MS) are more responsive to IFN-γ, corresponding to their brain-homing potential. We studied how a coding single nucleotide polymorphism (SNP) in IFNGR2 (rs9808753) co-operates with Epstein-Barr virus (EBV) infection as MS risk factors to affect the IFN-γ signaling pathway in human B cells. In both cell lines and primary cells, EBV infection positively associated with IFN-γ receptor expression and STAT1 phosphorylation. The IFNGR2 risk SNP selectively promoted downstream signaling via STAT1, particularly in transitional B cells. Altogether, EBV and the IFNGR2 risk SNP independently amplify IFN-γ signaling, potentially driving B cells to enter the MS brain.

Keywords: B cells; Epstein-Barr virus; IFNGR2; Multiple sclerosis; Risk SNP; rs9808753.

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Conflict of interest statement

Declaration of competing interest Marvin M. van Luijn received research support from EMD Serono, Merck, Novartis, GSK and Idorsia Pharmaceutical Ltd. Joost Smolders received lecture and/or consultancy fees from Biogen, Merck, Novartis, Sanofi-Genzyme and Roche. The remaining authors declare no competing interests.

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