Clinical and Immunological study of Rheumatoid Arthritis

青木等人。报道了用含有大量肠杆菌共同抗原(ECA)的热灭活大肠杆菌O：14超免疫诱导兔类风湿性关节炎，结果表明，高比例的诱导性关节炎动物也具有较高水平的E-Coli抗原抗体。因此，我们尝试用ELISA法分析类风湿关节炎患者血清和滑液中抗热致死E-COIL 0：14抗体的存在，并用免疫印迹分析和N-末端氨基酸分析方法检测类风湿关节炎患者血清和滑液中抗热致死E-COIL O：14抗体的抗原分子。与正常对照组比较，RA患者83份血清标本中33份血清和58份关节液标本中有33份抗热致死E线圈O：14抗体滴度显著升高。对类风湿关节炎患者标本的免疫印迹分析显示，不仅有与内毒素相关的ECA的梯状条带，而且有两条清晰的35 kDa(OmpA)和38 kDa(OMPC)的细菌外膜蛋白条带，与其他肠杆菌科细菌的氨基酸序列具有同源性。这些结果表明，这种对肠杆菌科常见抗原的敏感性可能在人类类风湿关节炎的发病机制中起着关键作用，类似于动物模型，一些类风湿关节炎患者对肠杆菌科常见的抗原敏感，这可能与未来类风湿关节炎免疫治疗的发展有关。

Aoki et al. reported the induction of RA-like arthritis in rabbits by hyperimmunisation with heat killed Escherichia coli (E coil) O : 14, which contains large amounts of enterobacterial common antigen (ECA), and showed that a high proportion of the animals with induced arthritis also had high levels of antibodies to the E coli antigen.The immunopathological similarities between the arthritic conditions induced in rabbits by hyper immunisations with E coil O : 14 and those in human RA have stimulated a search for an enterobacterial aetiology of the latter condition. Therefore, we tried to analyzed the presence of antibodies against heat killed E coil 0 : 14 in seerum and synovial fluid samples from patients with RA and control subjects including healthydonors and patients with osteoarthritis (OA) by ELISA and the antigenic molecules reacting with anti-E coil O : 14 antibodies from patients with RA using immunoblot analysis and N-terminal amino acid analysis. Compared with control subjects, patients with RA showed significantly increase titres of antibodies against heat killed E coil O : 14 in 33 of 83 serum samples and 38 of 58 joint fluid samples. Immunoblot analysis of the samples from RA patients revealed not only a ladder-like banding pattern equivalent to ECA associated with LPS, but also two clear bands of bacterial outer membrane protein of 35 kDa (OmpA) and 38 kDa (OmpC), having amino acid sequence homology with those of other Enterobacteriaceae.These results suggest that this sensitisation to antigens found commonly in Enterobacteriaceae may have a key role in pathogenesis of human RA similar to animal model, and some patients with RA are sensitised to antigens common to Enterobacteriaceae and this may prove relevant to the future development of immunotherapy for RA.