Assessment of programmed cell death 1 and its programmed cell death ligand 1 levels in vitiligo

Background Programmed cell death 1 (PD-1) is a cell surface protein that serves as an immune checkpoint in conjunction with its two ligands, PD-L1 and PD-L2. Recently, there has been a lot of interest in the role of the PD-1/PD-L1 pathway in immunoregulation. Objective To assess both PD-1 and PD-L1 levels in vitiligo patients' marginal and nonlesional biopsies compared with normal controls and to correlate them with disease parameters. Patients and methodsA total of 30 vitiliginous patients and 30 age and sex-matched controls were included. Full history and clinical examination were done and ELISA measured tissue levels of PD-1 and PD-L1 from lesional and nonlesional biopsies. Results Levels of tissue PD-1 in marginal biopsies (mean 7.89 +/- 2.48 ng/mg) were significantly higher than in nonlesional biopsies (mean 3.65 +/- 1.11 ng/mg; P<0.001) and significantly higher than the control PD-l level (mean 1.47 +/- 0.499 ng/mg; P<0.001). Nonlesional PD-1 level was also significantly higher than the control PD-l level (P<0.001). A statistically significant positive correlation was found between marginal and nonlesional PD-1 levels; (rho=0.792, P<0.001). Levels of tissue PD-L1 in marginal biopsies (mean 115 +/- 7.86 pg/mg) were significantly lower than in nonlesional skin (mean 194 +/- 8.12 pg/mg; P<0.001), and significantly lower than in controls (mean 283 +/- 27.8 pg/mg; P<0.001). Nonlesional PD-L1 level was also significantly lower than the control PD-Ll level (P<0.001). Conclusion Our results suggest that the PD-1/PD-L1 checkpoint seems to be implicated in the loss of peripheral tolerance in human vitiligo, with PD-1 being highly expressed, yet insufficiently stimulated due to lack of local PD-L1 expression. Since PD1 plays an important role, its agonists may have therapeutic implications in vitiligo and other autoimmune diseases but need wider-scale studies before clinical implementation.