33540 Altered expression of soluble and membrane-bound programmed death receptors and ligands may cause activated state of cytotoxic T lymphocytes in patients having alopecia areata

Abstract

Introduction: The occurrence of alopecia areata (AA) in cancer patients receiving programmed death (PD) inhibitors is known.(1) We assessed the expression of programmed death receptors (PD-1) and ligands (PDL-1) in patients with de novo AA. Methods: Forty consecutive patients with active patchy AA and 20 healthy controls were recruited. The expression of membrane-bound PD-1 (mPD-1) and PDL-1 (mPDL-1) was studied on the cytotoxic T-cells (Tc), type-1 helper T-cells (Th1) and activated regulatory T-cells (Tregs) in the peripheral blood of patients using cell specific markers through flow cytometry. Serum levels of soluble PD-1 and PDL-1 (sPD-1 and sPDL-1, respectively) were assessed using ELISA. Disease severity was assessed using severity of alopecia tool (SALT). Results: The mean SALT of our patients was 8.84 ± 11.47 with mean duration of illness being 12.12 ± 2.79 months. The percentage of Th1 and Tc was significantly higher in patients (P < .01 each) than healthy controls. Serum concentration of sPD-1 and sPDL-1 was significantly higher in patients than controls (P < .01 each). The expression of mPD-1 and mPDL-1 was significantly increased on Tc and Tregs respectively, of patients than controls (P < .01 and 0.001 respectively). A moderately significant correlation was seen between mPD-1 on Tc and sPD-1 (spearman rho 0.349, P < .01). None of the parameters demonstrated a significant correlation with SALT. Conclusion: Increased sPD-1 in AA patients probably saturates mPDL-1 on Tregs, thus increasing activity of Tc. Enhanced expression of mPD-1 and mPDL-1 on Tc and Tregs respectively, and increased sPDL-1 possibly represent a compensatory response to limit ongoing autoimmunity.