Overexpression of human homologs of the bacterial DnaJ chaperone in the synovial tissue of patients with rheumatoid arthritis

Abstract

Objective. To study the expression of the chaperone family of J proteins in the synovial tissue of patients with rheumatoid arthritis (RA) or osteoarthritis. Methods. Rabbit antibodies specific for a synthetic peptide (pHSJ1: EAYEVLSDKHKREIYD), representing the most conserved part of all J domains thus far identified-among them the Drosophila tumor suppressor Tid56-were used in immunohistochemical analyses of frozen sections of synovial tissue and immuno-blotting of protein extracts of adherent synovial cells. IgG specific for Tid56 was also used. Results. Both antisera predominantly and intensely stained synovial lining cells from RA patients; other cells did not stain or stained only faintly. In immunoblots, anti-pHSJ1 specifically detected several bands with molecular weights of >74 kd (type I), 57-64 kd (type II), 41-48 kd (type III), and <36 kd (type IV). The strongest band detected in RA adherent synovial cells was the type II band, whereas in a B cell line, a type I band was prominent. Conclusion. Several potentially new members of the J family are described. The type II band represents the human homolog of the Drosophila Tid56 protein and is strongly expressed in RA synovial tissue.

Hsp70 expression and induction as a readout for detection of immune modulatory components in food

“…Furthermore, DNAJ-like2 was one of the broadly expressed selfantigens that resulted in the development of CD4 + CD25 + regulatory T-cells after immunization of BALB/c mice (Nishikawa et al 2005). Also, enhanced expression of DNAJ family members in the synovial tissue of RA but OA patients has been found (Kurzik-Dumke et al 1999). These studies underlined that compounds acting on DNAJ and Fig.…”

The Human Endoplasmic Reticulum Molecular Chaperone BiP Is an Autoantigen for Rheumatoid Arthritis and Prevents the Induction of Experimental Arthritis

“…Human HSP60 (43) and human homologues of the bacterial chaperone DnaJ (44) are expressed in the rheumatoid synovial membrane. Although some investigators have provided evidence for preferential T cell responses by RA patients to mycobacterial hsp65 (45), the majority have been unable to do so (46,47).…”

Heat shock proteins (HSP) for immunotherapy of rheumatoid arthritis (RA)

“…DnaJp1 has several interesting characteristics that make it a good candidate for T cell epitope specific immunotherapy: (i): it belongs to an HSP that is highly antigenic; (ii) it induces cytokine production during the inflammation process; (iii) dnaJ human homologues are expressed in the inflamed synovium tissues [51] and may be part of the 'immunological dimmer' mechanism; (iv) as with other HSPs, it is highly conserved across species; (v) it has the 'shared epitope' sequence; (vi) it is also able triggers proinflammatory responses in T cells from RA patients, in a disease specific fashion [7]. This is a unique approach that allows a large field of possibilities.…”