Increased Expression of Glucocorticoid Receptorβ Messenger RNA in Patients with Ankylosing Spondylitis

BACKGROUND: Glucocorticoids have been known to be less effective for treating ankylosing spondylitis (AS) patients than for treating rheumatoid arthritis (RA) patients. To elucidate the mechanisms underlying this phenomenon, we evaluated whether the glucocorticoid receptor (GR)β expression of the peripheral blood mononuclear cells (PBMCs) in patients with AS is increased compared with patients with RA. METHODS: PBMCs were isolated from the subjects of 3 study groups: the healthy controls (n=25), the RA patients (n=25), and the AS patients (n=25). All the subjects had never taken corticosteroids and the patients with RA or AS were newly diagnosed. The expression of GRβ messenger RNA (mRNA) was determined by reverse transcription of the total RNA, and this was followed by semi-quantitative polymerase chain reaction analysis (RT-PCR). RESULTS: The level of GRα mRNA expression was not different among three groups. GRβ mRNA expression of the AS patients (2.02 [range: 0.99-7.21], median [25(th)-75(th) percentiles]) was enhanced compared with that of the controls (0.78 [range: 0.43-1.62]) and the RA patients (0.98 [range: 0.79-1.18]). The level of GRβ mRNA expression was not related to the inflammatory markers or the disease activity score 28 for the RA patients, and it was not related to the Bath ankylosing spondylitis disease activity index for the AS patients. CONCLUSION: The expression of GRβ mRNA, which is a dominant negative regulator for the glucocorticoid response, was increased in AS patients. The results suggest that the increased expression of GRβ mRNA may be related to the ineffectiveness of glucocorticoids for the treatment of AS.