title: Effects of methotrexate on the expression of the translational isoforms of glucocorticoid receptors α and β: correlation with methotrexate efficacy in rheumatoid arthritis patients.
abstract: OBJECTIVE
  To test the effect of MTX on the expression of glucocorticoid receptor (GR) α and β 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 GRα (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).
  
  
  CONCLUSIONS
  MTX in vitro induces greater expression of GRαAB 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.
authors.affiliation: Internal Medicine Department, Rheumatology Service, Clinical Hospital, Santiago, Chile.
authors.forename: Héctor
authors.initials: H
authors.lastname: Gatica
authors.forename: Marta
authors.initials: M
authors.lastname: Aliste
authors.forename: Julia
authors.initials: J
authors.lastname: Guerrero
authors.forename: Irmgadt Annelise
authors.initials: IA
authors.lastname: Goecke
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D002677:Chile; D004008:Diclofenac / Q000627:therapeutic use; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D020033:Protein Isoforms / Q000187:drug effects / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D005938:Glucocorticoids; D020033:Protein Isoforms; D011965:Receptors, Glucocorticoid; D004008:Diclofenac; D011239:Prednisolone; D008727:Methotrexate