Fibrin deimination in synovial tissue is not specific for rheumatoid arthritis but commonly occurs during synovitides
Fibrin deimination in synovial tissue is not specific for rheumatoid arthritis but commonly occurs during synovitides
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DOI：
10.4049/jimmunol.174.8.5057
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发表时间：
2005-04-15
影响因子：
4.4
通讯作者：
Serre, G
中科院分区：
文献类型：
--
作者：
Chapuy-Regaud, S;Sebbag, M;Serre, G
抗脱亚氨基（瓜氨酸化）蛋白的自身抗体是类风湿关节炎（RA）最特异的血清学标志物。脱亚胺化在产生它们识别的肽表位中至关重要。在滑膜组织（ST）中，纤维蛋白的α-和β-链的脱亚胺形式是其主要的自身抗原靶标（抗人纤维蛋白（原）自身抗体（AhFibA））。我们研究了ST中脱亚胺纤维蛋白的存在是否对RA具有特异性，因为这可以解释AhFibA为什么是RA特异性的。在13例RA患者和19例其他各种风湿性疾病患者中，在关节镜下识别的宏观炎症区域收集膝关节ST活检。滑膜炎的组织病理学证实，在所有的活检。通过免疫印迹，使用抗血清纤维蛋白，抗体瓜氨酸残基，和AhFibA纯化RA血清，脱亚胺纤维蛋白证明ST提取物从所有的患者。此外，观察到纤维蛋白脱亚胺化程度的变化与疾病无关。免疫组织化学分析，使用抗体的瓜氨酸残基和抗血清的ST相邻的连续切片的纤维蛋白，证实了这一结果，因为脱亚胺蛋白与纤维蛋白共定位在RA以及对照患者。因此，ST中的纤维蛋白脱亚氨基化是与任何滑膜炎相关的一般现象，其不一定诱导产生AhFibA的B自身免疫应答。
Autoantibodies to deiminated (citrullinated) proteins are the most specific serological markers of rheumatoid arthritis (RA). Deimination is critical in generating the peptidic epitopes they recognize. In the synovial tissue (ST), deiminated forms of the alpha-and beta-chains of fibrin are their major autoantigenic targets (anti-human fibrin(ogen) autoantibodies (AhFibA)). We investigated whether the presence of deiminated fibrin in the ST was specific for RA, because this could explain why AhFibA are RA specific. In 13 patients with RA and 19 patients with various other rheumatological disorders, knee ST biopsies were collected in macroscopically inflamed areas identified under arthroscopy. Synovitis was histopathologically confirmed in all of the biopsies. By immunoblotting, using antisera to fibrin, Abs to citrullyl residues, and AhFibA purified from RA sera, deiminated fibrin was evidenced in ST extracts from all of the patients. Moreover, variations in the degree of fibrin deimination were observed that were not related to the disease. Immunohistochemical analysis, using Abs to citrullyl residues and an antiserum to fibrin on adjacent serial sections of ST, confirmed the results because deiminated proteins colocalized with fibrin in RA as well as in control patients. Therefore, fibrin deimination in the ST is a general phenomenon associated to any synovitis, which does not necessarily induce a B autoimmune response with production of AhFibA.