Effects of methotrexate on the expression of the translational isoforms of glucocorticoid receptors alpha and beta: correlation with methotrexate efficacy in rheumatoid arthritis patients.

摘要

OBJECTIVES: To test the effect of MTX on the expression of glucocorticoid receptor (GR) alpha and beta isoforms AB, C and D in peripheral blood mononuclear cells (PBMCs) in culture, from newly diagnosed RA patients and to evaluate whether the test results correlate with patients' subsequent response to MTX treatment. METHODS: Twenty patients with early active RA were enrolled. Patients who had previously received any DMARD or cytotoxic agent, or who had received CSs in the 6 months before enrolment were excluded. PBMCs from all patients were obtained and cultured in the presence and absence of MTX (10(-4), 10(-6) and 10(-8) M). The expression of GR isoforms was evaluated by western blot. After blood samples were taken, patients entered a 24-week study receiving MTX, diclofenac and prednisone (10 mg/day). At Week 24, the ACR core set of disease activity measures was calculated and a correlation between the MTX effect on patients' PBMC GR expression in vitro and the ACR response was evaluated. RESULTS: MTX 10(-6) M in the culture medium induced the expression of the PBMC isoform AB of GRalpha (P = 0.009). Other GR isoforms were unaffected. The magnitude of the induced expression correlated with the ACR response to treatment at Week 24 of therapy (r = 0.92, P = 0.00003). CONCLUSION: MTX in vitro induces greater expression of GRalphaAB isoform in PBMC from RA patients who later respond to MTX treatment than in non-responding patients. This may have clinical applications for predicting MTX efficacy in RA patients.