Daily fingolimod administration may cause lymphopenia but alternate-day administration may be too little to inhibit disease activity

CD28/CTLA-4–CD80/CD86 molecules play an important role in the regulation of T cells activation. Defects in proteins involved in this pathway may lead to the development of autoimmune diseases in which T cells are involved. In this case–control study (336 multiple sclerosis (MS) patients and 322 controls) we investigated the possible association of eleven polymorphisms in CD28, CTLA-4, CD80 and CD86 genes with susceptibility to MS and/or its progression. We also took into account HLA-DRB1*15:01 status. Moreover, this study aimed to determinethe possible gene-gene interactions between examined SNPs associated with the susceptibility to MS and its outcome. Our investigation revealed that in HLA-DRB1*15:01 negative individuals, G allele in rs231775A NGof CTLA-4 gene was associatedwith higher risk ofmultiple sclerosis. Additionally, the association of rs2715267T NGof CD86 gene withMS susceptibilitywas detected. In details, carriers of G allele at this polymorphic site possessed higher risk of MS in comparison to TT homozygotes. On the other hand, the lower risk of MS was observed in individuals carrying A allele at the rs1599795T N A polymorphic site of CD80. Furthermore, the analysis revealed an interactionbetween three polymorphisms: rs3116496T N C (CD28), rs6641T N G (CD80) and rs17281995G N C (CD86), associated with the age of MS onset.