Increased expression of glucocorticoid receptor β in lymphocytes of patients with severe atopic dermatitis unresponsive to topical corticosteroid

Summary Background  Variable response to topical glucocorticoid therapy occurs in the treatment of severe atopic dermatitis (AD). Glucocorticoid receptor (GR)-β does not bind glucocorticoids but antagonizes the activity of the classic GRα, and could thus account for glucocorticoid insensitivity. Objectives  To investigate GRα and GRβ mRNA and protein expression in lymphocytes of patients with AD before and after treatment with topical corticosteroids. Methods  Blood was collected from 11 healthy donors, 10 patients with mild AD and 13 patients with severe AD. mRNA was isolated from peripheral blood mononuclear cells. Expression of GRα and GRβ mRNA was determined by reverse transcriptase–polymerase chain reaction and quantitated. Expression of the GRs was confirmed by Western blot analysis. Result  The expression of GRα mRNA was detected in all subjects. GRβ mRNA was detected in four out of 11 healthy volunteers, five out of 10 patients with mild AD and 11 out of 13 patients with severe AD. The incidence of GRβ mRNA expression was higher in patients with severe AD (85%) than in patients with mild AD (50%), and significantly higher than in healthy volunteers (36%, P = 0·033). Four of the 13 patients with severe AD showed a 3·3–13·2-fold increase in the expression of GRβ mRNA during a 2-week treatment with topical corticosteroids. In these patients the response to topical corticosteroids was poor. Conclusions  Expression of GRβ is increased during topical corticosteroid treatment in the lymphocytes of patients with AD and, in particular, glucocorticoid-insensitive AD is associated with increased expression of GRβ.