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

Human Hsp40 proteins, DNAJA1 and DNAJA2, as potential targets of the immune response triggered by bacterial DnaJ in rheumatoid arthritis.
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DOI:
10.1007/s12192-013-0407-1
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发表时间:
2013-09
影响因子:
3.8
通讯作者:
Lipinska, Barbara
Lipinska, Barbara
中科院分区:
生物学3区
文献类型:
--
作者:
Kotlarz, Agnieszka;Tukaj, Stefan;Krzewski, Konrad;Brycka, Elzbieta;Lipinska, Barbara

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细菌和人类来源的Hsp 40蛋白被怀疑参与类风湿性关节炎(RA)的发病机制。已经显示RA患者的血清含有针对细菌和人Hsp 40的增加水平的抗体。这项工作的目的是探索细菌(DnaJ)和人类(DNAJA 1和DNAJA 2)Hsp 40蛋白之间的免疫相似性,以及它们可能参与RA的关系。使用针对全长DnaJ或其结构域、针对DNAJA 1和DNAJA 2以及单克隆抗DnaJ抗体的多克隆抗体,我们发现细菌和人Hsp 40之间的免疫相似性。ELISA和Western blotting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。我们还发现RA患者血清中抗DNAJ和抗DNAJA 1抗体水平之间呈正相关。这一发现支持了分子模拟假说,即人Hsp 40可能是最初针对RA中细菌DnaJ的抗体的靶标。本文的在线版本(doi:10.1007/s12192-013-0407-1)包含补充材料,可供授权用户使用。
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. The online version of this article (doi:10.1007/s12192-013-0407-1) contains supplementary material, which is available to authorized users.
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