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

Agnieszka Kotlarz,Elzbieta Brycka,Konrad Krzewski,Barbara Lipinska,Stefan Tukaj

doi:10.1007/s12192-013-0407-1

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s12192-013-0407-1) contains supplementary material, which is available to authorized users.

Highlights

Heat shock proteins (Hsps) are a family of evolutionarily conserved proteins, which play an important role in cell physiology under the normal and stress conditions
The Hsps of the Hsp60 and Hsp70 families were the ones most extensively studied, especially since the discovery that the T cells isolated from the rats with adjuvant-induced arthritis were responding to mycobacterial Hsp60
Polyclonal antibodies against DnaJ, N-DnaJ, and C-DnaJ react with human DNAJA1 and DNAJA2

Summary

Introduction

Heat shock proteins (Hsps) are a family of evolutionarily conserved proteins, which play an important role in cell physiology under the normal and stress conditions. Hsps are a group of major bacterial antigens (Albani et al 1995; reviewed in Borges et al 2012), and the conservation of their structure from bacteria to man, as well as high immunogenicity, makes them attractive targets for investigation in the area of autoimmunity. In this area, the Hsps of the Hsp and Hsp families were the ones most extensively studied, especially since the discovery that the T cells isolated from the rats with adjuvant-induced arthritis were responding to mycobacterial Hsp (van Eden et al 1988; reviewed in van Eden et al 2005).

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