Mertz A K, Batsford S R, Curschellas E, Kist M J, Gondolf K B
Department of Immunology, University of Freiburg, Federal Republic of Germany.
J Clin Invest. 1991 Aug;88(2):632-42. doi: 10.1172/JCI115348.
Cationic antigens are known to have considerable arthritogenic potential in experimental systems. During a systematic search for suitable, naturally occurring candidates an intracellular protein was isolated from the ribosomal pellet of Yersinia enterocolitica 0:3, a bacterial strain associated with reactive arthritis in humans. The protein is highly cationic, contains two 19-kD polypeptide chains linked by a disulfide bond, and reveals a strong tendency for spontaneous aggregation. It is suggested to be a nucleic acid binding protein. We tested this antigen for its ability to induce arthritis after intra-articular challenge in preimmunized rats. An acute inflammatory phase followed by transition to chronicity was observed both by technetium-99m scintigraphy and from histology. Massive polymorphonuclear leucocyte infiltration of the synovium was seen early on and fibrosis and thickening of the joint capsule occurred in later stages. Control groups showed no evidence of inflammation. Western blot and ELISA analysis of unselected sera from Yersinia enterocolitica 0:3-infected patients revealed antibodies to the antigen in the majority of cases, whereas healthy individuals rarely reacted. This is the first report of a naturally occurring cationic antigen capable of inducing immunologic tissue injury; it justifies the speculation that cationic antigens from prokaryotic cells could trigger reactive arthritis in humans.
已知阳离子抗原在实验系统中具有相当大的致关节炎潜力。在对合适的天然存在的候选物进行系统搜索过程中,从与人类反应性关节炎相关的细菌菌株小肠结肠炎耶尔森菌0:3的核糖体沉淀中分离出一种细胞内蛋白质。该蛋白质高度带正电荷,包含两条通过二硫键连接的19-kD多肽链,并显示出强烈的自发聚集倾向。它被认为是一种核酸结合蛋白。我们在预先免疫的大鼠中进行关节内攻击后,测试了这种抗原诱导关节炎的能力。通过锝-99m闪烁扫描和组织学观察到先是急性期,随后转变为慢性期。早期可见滑膜大量多形核白细胞浸润,后期关节囊出现纤维化和增厚。对照组未显示炎症迹象。对小肠结肠炎耶尔森菌0:3感染患者未筛选血清进行的蛋白质印迹和ELISA分析显示,大多数病例中存在针对该抗原的抗体,而健康个体很少有反应。这是关于一种能够诱导免疫组织损伤的天然存在的阳离子抗原的首次报道;这证明了原核细胞的阳离子抗原可能引发人类反应性关节炎这一推测的合理性。