Rheumatology Advance Access published online on October 13, 2006
Rheumatology, doi:10.1093/rheumatology/kel276
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1 Bone & Joint Research Unit, Barts and The London, Queen Mary's School of Medicine & Dentistry, University of London, Charterhouse Square, London EC1M 6BQ, UK; Present address: Adnan Menderes University, School of Medicine, Department of Biochemistry, Aydin 09100, Turkey.
* To whom correspondence should be addressed. Objective. A proportion of patients with rheumatoid arthritis (RA) fail to respond adequately to corticosteroid (CS) therapy. Using an in vitro CS sensitivity bioassay, we have subdivided RA patients into steroid-sensitive (SS) and -resistant (SR) subgroups and this correlates with clinical responses to CS therapy. CSs exert their effects via the CS receptor (CR), which exists as two main isoforms, CR Methods. Peripheral blood mononuclear cells (PBMCs) were isolated from SS and SR RA patients. CR Results. qRT-PCR analysis showed a trend towards higher expression of both CR Conclusion. We show for the first time that CR
Received October 25, 2005
Accepted July 4, 2006
Original Papers
The differential expression of corticosteroid receptor isoforms in corticosteroid-resistant and -sensitive patients with rheumatoid arthritis
D. L. Kozaci 1, Y. Chernajovsky 2, and I. C. Chikanza 3 *
2 Bone & Joint Research Unit, Barts and The London, Queen Mary's School of Medicine & Dentistry, University of London, Charterhouse Square, London EC1M 6BQ, UK.
3 Bone & Joint Research Unit, Barts and The London, Queen Mary's School of Medicine & Dentistry, University of London, Charterhouse Square, London EC1M 6BQ, UK; Department of Rheumatology, Barts & The Royal London and Newham University Hospitals, London, UK.
I. C. Chikanza, E-mail: icchikanza{at}sachicorp.net
Abstract 
and CR
. CR can function as a negative inhibitor of CR. We have hypothesized that steroid resistance in RA patients is due in part to a relative over-expression of the CR. and CR mRNA expression was determined by quantitative real time polymerase chain reaction (qRT-PCR). The ratio of CR/CR mRNA expression was determined. CR and CR protein expression by PBMCs was analysed by flow cytometry. and basal CR/CR ratio in SR RA patients. Stimulation of PBMCs in vitro with concanavalin-A induced a significantly higher CR mRNA expression, and CR/CR ratio in SR RA patients compared with SS patients, which was not inhibited by hydrocortisone. Flow cytometry showed that the percentage of PBMCs staining for CR protein was significantly lower in the SS RA group (SS 43.3 ± 14.8% vs SR 88.6 ± 8.6%; P < 0.0010). The mean intensity of fluorescence CR staining was higher in the SR RA patients (P < 0.001). is over-expressed in SR RA patients and that hydrocortisone fails to inhibit concanavalin-A stimulated increase in CR mRNA in SR RA patients. This mechanism may contribute in part to the CS hyporesponsiveness seen in some RA patients.
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