Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease in Western countries. Although topical and/or systemic glucocorticoids treatment efficacy is widely recognized, up to 30% of BP patients may undergo a relapse during the first year of treatment. In this study, we investigated the protein expression of the total glucocorticoid receptor and GRβ isoform in the skin biopsy specimens from BP patients (n=23, mean age 78.6 ± 15.8, 12 females and 11 males) and from 14 controls (7 females and 7 males; patients without inflammatory and autoimmune diseases). In the aim to relate GR expression to disease outcome, total GR and GRβ protein expressions were analysed at baseline by immunohistochemistry in 12 BP patients who later relapsed and 11 BP patients who remained on remission during the first year of treatment. Compared with controls, the expression of total GR in the keratinocytes of patients with BP was significantly lower (P<0.001). This decrease was also observed in both cellular compartments, the cytoplasm (P<0.01) and the nucleus (P<0.001). Also, a significant increase of GRβ labelling was observed in the nuclear compartment (P<0.001) but not in the cytoplasm keratonocytes. Furthermore, total GRβ keratinocytes expression was significantly higher in BP patients who relapse under therapy during the first year of follow up than in BP patients with ongoing remission (P<0.05). Thus, our results suggest that increased protein expression of GRβ in the skin epithelial keratinocytes of BP patients is predictive of reduced steroid treatment efficacy, and therefore of increased risk of disease relapse on therapy.

Variation of the epidermal expression of glucocorticoid receptor-beta as predictive marker of bullous pemphigoid outcome