Heat shock protein gene expression profile may differentiate between rheumatoid arthritis, osteoarthritis, and healthy controls

Abstract

Objective: Heat shock proteins (Hsps) have been repeatedly implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this work was to study Hsp mRNA and protein levels to determine whether they can be used to differentiate between RA, osteoarthritis (OA), and healthy controls.

Methods: Hsp27, Hsp60, Hsp70, Hsp90α, and HspBP1 mRNA expression was analysed using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 24 RA, 11 OA, and 21 healthy controls. Hsp70 and HspBP1 protein levels were measured in serum using an enzyme-linked immunosorbent assay (ELISA).

Results: Hsp gene expression profiles differ significantly between inflammatory (RA) and non-inflammatory (OA) joint diseases, showing significantly increased Hsp27 and Hsp90α mRNA levels in RA synovial tissues. Up-regulated Hsp60 and Hsp90α together with down-regulated Hsp70 and elevated HspBP1/Hsp70 mRNA ratios can be used to differentiate between RA patients and healthy individuals through analysis of peripheral blood samples. Despite increased HspBP1 levels in RA sera, Hsp70 levels and the HspBP1/Hsp70 protein ratio remained identical in the RA patients and healthy individuals, which may contribute to the inhibition of Hsp70 anti-apoptotic activity.

Conclusion: Hsp gene expression analysis can be implemented as a new diagnostic approach to facilitate differentiation between RA, OA, and healthy controls.

Acknowledgements

We thank Associate Professor Stanislav Popelka, Dr David Veigl, and Associate Professor Jan Pech, from The First Clinic of Orthopaedics, University Hospital Motol, Prague, for providing tissue samples and their kind collaboration. We would also thank Roman Volchenkov (currently at The Gade Institute, University of Bergen, Norway), who was employed from April 2008 to June 2009 as an early stage researcher on the TRANSNET project, for his participation in the designing and testing of TaqMan systems for the detection of Hsps. Thanks also to Zuzana Imryskova, who participated in testing of patients with osteoarthritis. This project was supported by TRANSNET (No. MRTN-CT-2004-512253) and STEMDIAGNOSTICS (No. LSHB-CT-2007-037703).