{Reference Type}: Journal Article
{Title}: Impact of coding risk variant IFNGR2 on the B cell-intrinsic IFN-γ signaling pathway in multiple sclerosis.
{Author}: Bogers L;Rip J;Rijvers L;van Langelaar J;Koetzier SC;Kuiper KL;Meerdink V;Wierenga-Wolf AF;Melief MJ;Marques AM;Smolders J;van Luijn MM;
{Journal}: J Autoimmun
{Volume}: 148
{Issue}: 0
{Year}: 2024 Jul 6
{Factor}: 14.511
{DOI}: 10.1016/j.jaut.2024.103279
{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.