The human endoplasmic reticulum molecular chaperone BiP is an autoantigen for rheumatoid arthritis and prevents the induction of experimental arthritis
The human endoplasmic reticulum molecular chaperone BiP is an autoantigen for rheumatoid arthritis and prevents the induction of experimental arthritis
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DOI：
10.4049/jimmunol.166.3.1492
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发表时间：
2001-02-01
影响因子：
4.4
通讯作者：
Panayi, GS
中科院分区：
文献类型：
--
作者：
Corrigall, VM;Bodman-Smith, MD;Panayi, GS
类风湿性关节炎（RA）是最常见的致残人类自身免疫性疾病。使用Western blotting和串联质谱技术，我们已经确定了内质网伴蛋白BiP，一种78 kda的葡萄糖调节蛋白，作为一种可能的自身抗原，它优先刺激RA患者滑膜T细胞的增殖增加，而不是其他关节炎患者。已建立胶原或蛋白酶诱导关节炎的小鼠对BiP产生IgG抗体。虽然经CFA注射的BiP在包括HLA-DR4（+/-）和HLA-DR1(+/+)-转基因动物在内的多株大鼠和小鼠中均未能诱导关节炎，但在注射II型胶原关节炎前1周静脉注射BiP可完全抑制关节炎的发展。BiP预免疫以类似的方式抑制Lewis大鼠佐剂性关节炎的发展。这是首次报道在人类类风湿性关节炎和实验性关节炎中，哺乳动物伴侣蛋白是一种自身抗原，也可以防止实验性关节炎的诱导。这些发现可能会刺激开发新的免疫疗法治疗类风湿性关节炎。
Rheumatoid arthritis (RA) is the most common, crippling human autoimmune disease. Using Western blotting and tandem mass spectroscopy, we have identified the endoplasmic reticulum chaperone BiP, a 78-kDa glucose-regulated protein, as a possible autoantigen, It preferentially stimulated increased proliferation of synovial T cells from patients with RA but not from patients with other arthritides. Mice with established collagen- or pristane-induced arthritis developed IgG Abs to BiP. Although BiP injected in CFA failed to induce arthritis in several strains of rats and mice, including HLA-DR4(+/-) and HLA-DR1(+/+)-transgenic animals, it completely inhibited the development of arthritis when given i.v. 1 wk before the injection of type II collagen arthritis. Preimmunization with BiP suppressed the development of adjuvant arthritis in Lewis rats in a similar manner. This is the first report of a mammalian chaperone that is an autoantigen in human RA and in experimental arthritis and that can also prevent the induction of experimental arthritis. These findings may stimulate the development of new immunotherapies for the treatment of RA.