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

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          Abstract

          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.

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          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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          Most cited references21

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          Heat-shock proteins induce T-cell regulation of chronic inflammation.

          Immune responses to certain heat-shock proteins (HSPs) develop in almost all inflammatory diseases; however, the significance of such responses is only now becoming clear. In experimental disease models, HSPs can prevent or arrest inflammatory damage, and in initial clinical trials in patients with chronic inflammatory disease, HSP-derived peptides have been shown to promote the production of anti-inflammatory cytokines, indicating that HSPs have immunoregulatory potential. In this Review, we discuss the unique characteristics of HSPs that endow them with these immunoregulatory qualities.
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            Structure, function and evolution of DnaJ: conservation and adaptation of chaperone function.

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              Periodontitis in RA-the citrullinated enolase connection.

              Autoimmunity in rheumatoid arthritis (RA) is characterized by an antibody response to citrullinated proteins. Two of the risk factors for RA-HLA-DRB1 shared epitope alleles and smoking-are also associated with periodontitis, which is largely, but not exclusively, caused by Porphyromonas gingivalis infection. Furthermore, RA and periodontitis have a similar pathophysiology, characterized by destructive inflammation. The citrullination of proteins by P. gingivalis and the subsequent generation of autoantigens that drive autoimmunity in RA represents a possible causative link between these two diseases. Antibodies directed towards the immunodominant epitope of human citrullinated α-enolase cross-react with a conserved sequence on citrullinated P. gingivalis enolase. On the basis of this cross-reactivity, in this Perspectives article we explore the hypothesis of molecular mimicry in the etiology of RA, with citrullinated enolase as the specific antigen involved.
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                Author and article information

                Contributors
                +48-58-5236310 , +48-58-5236309 , lipinska@biotech.ug.gda.pl
                Journal
                Cell Stress Chaperones
                Cell Stress Chaperones
                Cell Stress & Chaperones
                Springer Netherlands (Dordrecht )
                1355-8145
                1466-1268
                14 February 2013
                14 February 2013
                September 2013
                : 18
                : 5
                : 653-659
                Affiliations
                [ ]Department of Biochemistry, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland
                [ ]Department of Plant Physiology and Biotechnology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland
                [ ]Department of Molecular Virology, University of Gdansk and Medical University of Gdansk, Kladki 24, 80-822 Gdansk, Poland
                [ ]National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD USA
                Article
                407
                10.1007/s12192-013-0407-1
                3745263
                23408083
                5234f085-f3c5-49f6-849a-ae0c1906c3e9
                © The Author(s) 2013

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                : 11 December 2012
                : 23 January 2013
                : 24 January 2013
                Categories
                Short Communication
                Custom metadata
                © Cell Stress Society International 2013

                Molecular biology
                anti-hsp40 autoantibodies,hsp40 in rheumatoid arthritis,cross-reactivity of anti-hsp40 antibodies,anti-dnaj monoclonal antibodies,molecular mimicry

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