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Human Hsp40 proteins DNAJA1 and DNAJA2 as potential targets of the immune response triggered by bacterial DnaJ in rheumatoid arthritis

机译:人类Hsp40蛋白DNAJA1和DNAJA2作为类风湿关节炎细菌DnaJ触发的免疫应答的潜在靶标

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摘要

Hsp40 proteins of bacterial and human origin are suspected to be involved in the pathogenesis of rheumatoid arthritis (RA). It has been shown that sera of RA patients contain increased levels of antibodies directed to bacterial and human Hsp40s. The aim of this work was to explore immunological similarities between the bacterial (DnaJ) and human (DNAJA1 and DNAJA2) Hsp40 proteins in relation to their possible involvement in the RA. Using polyclonal antibodies directed against a full-length DnaJ or its domains, against DNAJA1 and DNAJA2, as well as monoclonal anti-DnaJ antibodies, we found immunological similarities between the bacterial and human Hsp40s. Both ELISA and Western blotting showed that these similarities were not restricted to the conserved J domains but were also present in the C-terminal variable regions. We also found a positive correlation between the levels of the anti-DnaJ and anti-DNAJA1 antibodies in the sera of RA patients. This finding supports the molecular mimicry hypothesis that human Hsp40 could be the targets of antibodies originally directed against bacterial DnaJ in RA.Electronic supplementary materialThe online version of this article (doi:10.1007/s12192-013-0407-1) contains supplementary material, which is available to authorized users.
机译:细菌和人类来源的Hsp40蛋白被怀疑与类风湿关节炎(RA)的发病机理有关。已经显示,RA患者的血清含有针对细菌和人Hsp40的抗体水平升高。这项工作的目的是探讨细菌(DnaJ)和人(DNAJA1和DNAJA2)Hsp40蛋白之间可能与RA相关的免疫学相似性。使用针对全长DnaJ或其域,针对DNAJA1和DNAJA2的多克隆抗体以及单克隆抗DnaJ抗体,我们发现了细菌和人类Hsp40之间的免疫学相似性。 ELISA和蛋白质印迹法均表明,这些相似性不仅限于保守的J结构域,而且还存在于C末端可变区中。我们还发现RA患者血清中的抗DnaJ和抗DNAJA1抗体水平呈正相关。这一发现支持了分子模拟假说,即人类Hsp40可能是RA中最初针对细菌DnaJ的抗体的靶标。电子补充材料本文的在线版本(doi:10.1007 / s12192-013-0407-1)包含补充材料,其中适用于授权用户。

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