Lack of involvement of P-glycoprotein (P-gp) in pemphigus patients with poor response to steroid therapy.

A small but significant fraction of pemphigus patients do not show an adequate response to steroid therapy. P-glycoprotein (or P-gp) is a cell membrane efflux pump that expels drugs, including glucocorticoids, from the cytosol to the extracellular medium. An increased expression and/or function of P-glycoprotein in lymphoid cells could decrease the intracellular concentration of glucocorticoids, diminishing its therapeutic effects. The aim of this work was to assess the expression and activity of P-glycoprotein in the mononuclear cells (MNC) from pemphigus patients with good and poor response to steroid therapy. We studied 20 patients with pemphigus vulgaris, eight of them classified as poor responders and 12 as good responders to steroid therapy. The expression and activity of P-glycoprotein by MNC were quantified by flow cytometry, and P-glycoprotein mRNA levels were determined by a semi-quantitative RT-PCR technique. We found that the expression of P-glycoprotein at both mRNA and protein levels was similar in pemphigus patients with good and poor response to steroid therapy. Similar results were obtained regarding P-glycoprotein activity. P-glycoprotein does not seem to be involved in the poor response to steroid treatment seen in some pemphigus patients. It is important to investigate additional mechanisms that could account for the glucocorticoid resistance seen in some pemphigus patients.