Rheumatoid arthritis, Proteus, anti-CCP antibodies and Karl Popper
Rheumatoid arthritis, Proteus, anti-CCP antibodies and Karl Popper
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DOI：
10.1016/j.autrev.2009.10.006
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发表时间：
2010-02-01
影响因子：
13.6
通讯作者：
Wilson, Clyde
中科院分区：
文献类型：
--
作者：
Ebringer, Alan;Rashid, Taha;Wilson, Clyde
风湿性关节炎（RA）是一种严重的关节疾病，影响全球超过2000万人。RA的病因很可能与微生物触发、遗传关联和自身免疫三联体有关，并且可以使用卡尔·波普尔或波普尔序列的哲学方法来解释。10个“波普尔序列”已经被确定，指出泌尿微生物奇异变形杆菌是RA的原因：波普尔序列I确定了注射到兔子体内的HLA-DR 4淋巴细胞引起针对变形杆菌的特异性抗体。Popper序列2确定了来自14个不同国家的RA患者中存在变形杆菌的抗体。Popper序列3确定RA患者中的变形杆菌属细菌的抗体是疾病特异性的，因为在其他条件下没有发现这样的抗体。Popper序列4确定，当RA患者具有高滴度的变形杆菌抗体时，在尿培养物中发现这种细菌。Popper序列5确定了只有变形杆菌属细菌而没有其他微生物在RA患者中引起显著升高的抗体。Popper序列6确定了“共享表位”EQR（K）RAA显示与变形杆菌溶血素中发现的序列ESRRAL的“分子模拟”。Popper序列7确定变形杆菌尿素酶含有序列IRRET，其与透明软骨的胶原蛋白XI中发现的LRREI具有“分子模拟”。Popper序列8证实，从RA患者获得的血清对包被有交叉反应性EQR（K）RAA和LRREI自身抗原肽的绵羊红细胞具有致细胞病变性质。Popper序列9确定了溶血素和尿素酶以及自身抗原HLA-DR 1/4和胶原蛋白XI中的变形杆菌序列。每一个都含有精氨酸双联体，从而为肽基精氨酸脱亚胺酶（PAD）提供底物，以产生瓜氨酸，瓜氨酸是CCP的主要抗原成分，在RA的早期病例中发现了CCP的抗体。Popper序列10证实，变形杆菌的抗体不仅来自与自身抗原交叉反应的序列，而且来自非交叉反应序列，从而表明活动性RA患者已暴露于变形杆菌感染。10个Popper序列确定RA最有可能是由变形杆菌属上尿路感染引起的，这可能可以用抗变形杆菌治疗。(C)2009 Elsevier B. V.保留所有权利目录
Rheumatoid arthritis (RA) is a crippling joint disease affecting over 20 million people worldwide. The cause of RA is most probably linked to the triad of microbial trigger, genetic association and autoimmunity and can be explained using the philosophical method of Karl Popper or Popperian sequences. Ten "Popper sequences" have been identified which point to the urinary microbe Proteus mirabilis as the cause of RA: Popper sequence I establishes that HLA-DR4 lymphocytes injected into a rabbit evoke specific antibodies against Proteus bacteria. Popper sequence 2 establishes that antibodies to Proteus bacteria are present in RA patients from 14 different countries. Popper sequence 3 establishes that antibodies to Proteus bacteria in RA patients are disease specific since no such antibodies are found in other conditions. Popper sequence 4 establishes that when RA patients have high titres; of antibodies to Proteus such bacteria are found in urinary cultures. Popper sequence 5 establishes that only Proteus bacteria and no other microbes evoke significantly elevated antibodies in RA patients. Popper sequence 6 establishes that the "shared epitope" EQR(K)RAA shows, "molecular mimicry" with the sequence ESRRAL found in Proteus haemolysin. Popper sequence 7 establishes that Proteus urease contains a sequence IRRET which has "molecular mimicry" with LRREI found in collagen XI of hyaline cartilage. Popper sequence 8 establishes that sera obtained from RA patients have cytopathic properties against sheep red cells coated with the cross-reacting EQR(K)RAA and LRREI self-antigen peptides. Popper sequence 9 establishes that Proteus sequences in haemolysin and urease as well as the self antigens, HLA-DR1/4 and collagen XI. each contain an arginine doublet, thereby providing a substrate for peptidyl arginine deiminase (PAD) to give rise to citrulline, which is the main antigenic component of CCP, antibodies to which are found in early cases of RA. Popper sequence 10 establishes that antibodies to Proteus come not only from sequences crossreacting to self antigens but also from non-crossreacting sequences, thereby indicating that active RA patients have been exposed to infection by Proteus. The ten Popper sequences establish that RA is most probably caused by Proteus upper urinary tract infections, which can possibly be treated with anti-Proteus therapy. (C) 2009 Elsevier B.V. All rights reserved Contents