Simultaneous evaluation of in vivo glucocorticoid sensitivity and expression of glucocorticoid receptor alpha-isoform in rheumatoid arthritis patients

To analyze glucocorticoid (GC) sensitivity using intravenous very low dose dexamethasone suppression test (IV-VLD-DST) in patients with rheumatoid arthritis (RA) and its correlation with glucocorticoid receptor alpha-isoform (GRalpha) gene expression. We evaluated 20 healthy controls and 32 RA patients with Health Assessment Questionnaire (HAQ) and Disease Activity Score 28 joints (DAS) scores and IV-VLD-DST and GRalpha expression in mononuclear cells. Basal cortisol and the percentage of cortisol reduction after IV-VLD-DST were lower in RA patients than in controls, whereas GRalpha expression was similar among groups. In the RA group there was an inverse correlation between GRalpha expression and the percentage of cortisol suppression that was not observed in controls. There was a direct relationship between DAS and GRalpha expression. Mechanisms involved in GC resistance observed in patients with RA are possibly not at the level of GRalpha gene expression, since it was similar among groups and GRalpha increased with disease activity.