A functional polymorphism in B and T lymphocyte attenuator is associated with susceptibility to rheumatoid arthritis.
A functional polymorphism in B and T lymphocyte attenuator is associated with susceptibility to rheumatoid arthritis.
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DOI：
10.1155/2011/305656
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发表时间：
2011
影响因子：
--
通讯作者：
Nakajima H
中科院分区：
文献类型：
--
作者：
Oki M;Watanabe N;Owada T;Oya Y;Ikeda K;Saito Y;Matsumura R;Seto Y;Iwamoto I;Nakajima H
抑制性辅助受体被认为在维持免疫稳态中起重要作用，并且抑制性辅助受体的负性信号的缺陷可能导致自身免疫性疾病的发展。我们最近已经确定了B和T淋巴细胞衰减剂（BTLA），一种新的抑制性辅助受体表达的免疫细胞，我们认为，BTLA可能参与发展的自身免疫性疾病，使用BTLA缺陷小鼠。然而，BTLA在人类自身免疫性疾病发病机制中的作用仍然未知。因此，我们通过进行病例对照遗传关联研究，检查BTLA与类风湿性关节炎（RA）、系统性红斑狼疮（SLE）和干燥综合征（SS）之间的可能关联。BTLA基因590 C单核苷酸多态性（SNP）与RA的易感性相关，与SLE、SS的易感性无关。此外，携带该590 C SNP的RA患者比不携带该等位基因的患者更早发生疾病。我们还发现带有590 C等位基因的BTLA对伴刀豆球蛋白A和抗CD 3抗体诱导的Jurkat T细胞IL-2产生缺乏抑制活性。这些结果表明，BTLA是RA易感基因，并参与保护人类自身免疫。
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.
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影响因子：
16.8
作者：
Croft, M
通讯作者：
Croft, M
影响因子：
30.5
作者：
Latchman, Y;Wood, CR;Freeman, GJ
通讯作者：
Freeman, GJ
影响因子：
--
作者：
Kochi, Y;Yamada, R;Yamamoto, K
通讯作者：
Yamamoto, K
影响因子：
--
作者：
Oya, Yoshihiro;Watanabe, Norihiko;Owada, Takayoshi;Oki, Mie;Hirose, Koichi;Suto, Akira;Kagami, Shin-ichiro;Nakajima, Hiroshi;Kishimoto, Takashi;Iwamoto, Itsuo;Murphy, Theresa L.;Murphy, Kenneth M.;Saito, Yasushi
通讯作者：
Saito, Yasushi
影响因子：
4.4
作者：
Hurchla, MA;Sedy, JR;Murphy, KM
通讯作者：
Murphy, KM