title: Daily fingolimod administration may cause lymphopenia but alternate-day administration may be too little to inhibit disease activity.
abstract: 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.
authors.affiliation: Multiple sclerosis center, Utano National Hospital, 8 Ondoyama, Narutaki, Ukyo-ku, Kyoto 616-8255, Japan. Electronic address: nra17777@nifty.com.
authors.forename: Masami
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Neurology, Utano National Hospital, 8 Ondoyama, Narutaki, Ukyo-ku, Kyoto 616-8255, Japan. Electronic address: machakok@unh.hosp.go.jp.
authors.forename: Masako
authors.initials: M
authors.lastname: Kinoshita
mesh_terms: D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000188:drug therapy*; D011409:Propylene Glycols / Q000008:administration & dosage*; D013110:Sphingosine / Q000031:analogs & derivatives*
chemical_list: D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D013110:Sphingosine
keywords: Fingolimod; Multiple sclerosis; alternate-day administration; lymphopenia; relapses