title: A functional polymorphism in B and T lymphocyte attenuator is associated with susceptibility to rheumatoid arthritis.
abstract: Inhibitory coreceptors are thought to play important roles in maintaining immunological homeostasis, and a defect in the negative signals from inhibitory coreceptors may lead to the development of autoimmune diseases. We have recently identified B and T lymphocyte attenuator (BTLA), a new inhibitory coreceptor expressed on immune cells, and we suggest that BTLA may be involved in the development of autoimmune diseases using BTLA-deficient mice. However, the role of BTLA in the pathogenesis of autoimmune diseases in humans remains unknown. We, therefore, examined the possible association between BTLA and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS) by conducting a case-control genetic association study. We found that 590C single-nucleotide polymorphism (SNP) of BTLA gene was significantly associated with susceptibility to RA, but not to SLE or SS. Furthermore, RA patients bearing this 590C SNP developed the disease significantly earlier than the patients without this allele. We also found that BTLA with 590C allele lacked the inhibitory activity on concanavalin A- and anti-CD3 Ab-induced IL-2 production in Jurkat T cells. These results suggest that BTLA is an RA-susceptibility gene and is involved in the protection from autoimmunity in humans.
authors.affiliation: Department of Allergy and Clinical Immunology, Chiba University Hospital, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Oki
authors.forename: Norihiko
authors.initials: N
authors.lastname: Watanabe
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Owada
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oya
authors.forename: Kei
authors.initials: K
authors.lastname: Ikeda
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Matsumura
authors.forename: Yohei
authors.initials: Y
authors.lastname: Seto
authors.forename: Itsuo
authors.initials: I
authors.lastname: Iwamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakajima
mesh_terms: D000483:Alleles; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D001402:B-Lymphocytes; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D007564:Japan; D019169:Jurkat Cells; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008213:Lymphocyte Activation / Q000502:physiology; D008297:Male; D051379:Mice; D020641:Polymorphism, Single Nucleotide; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics; D012859:Sjogren's Syndrome / Q000235:genetics*; D013601:T-Lymphocytes
chemical_list: C482586:BTLA protein, human; D007376:Interleukin-2; D011971:Receptors, Immunologic