Aberrant expression of the co-chaperone HDJ2 in rheumatoid arthritis

Background

HDJ2 is among approximately 98 human DnaJ homologues listed in protein databases. DnaJ homologues cooperate with HSP70 chaperones, which regulate protein conformation under stress as well as normal physiological conditions. Functions of the HSP70 chaperone machinery include destruction and repair of misfolded proteins. We previously observed that several DnaJ homologs are differentially expressed in synovial tissue of patients with rheumatoid arthritis (RA).

Objective

HDJ2 is one of the few DnaJ homologues that can be detected specifically as protein and mRNA. We therefore wished to evaluate its expression on both levels in material derived from RA patients or healthy donors (HD).

Methods

Synovial tissue (ST) from RA patients and appropriate controls was stained with a specific monoclonal antibody (immunohistochemistry). The expression of HDJ2 was characterized in peripheral blood (PB) mononuclear cells (MNC) from HD; PBMNC from RA patients; and MNC from synovial fluid (SFMNC) and ST from RA patients. PB and SF leukocytes isolated by density gradient centrifugation were separated in monocytes (MC), remaining mononuclear cells (nonMC) and granulocytes. Cell populations were analyzed for HDJ2 expression by FACS and RT-PCR.

Results

HDJ2 mRNA was expressed in PBMNC of HD. Separation of PBMNC in MC and nonMC showed HDJ2 mRNA in both populations. HDJ2 protein was detected intracellularly in PBMNC of HD by FACS analysis, with stronger signals in MC than in nonMC. PBMNC derived from HD and RA patients did not show any surface expression of HDJ2. PB and SF leukocytes from RA patients varied in their HDJ2 mRNA expression between presence and absence. HDJ2 protein was overexpressed in RA ST and detected on the cell surface of RA SFMNC.

Conclusions

HDJ2 mRNA and protein expression are regulated differentially. More patients must be analyzed to describe possible correlations between expression patterns and other parameters and to understand the function of synovial HDJ2 expression.