Sherif S Awad1, Ahmed A Touni1, Manal Y Gabril2. 1. Department of Dermatology and Venereology, Faculty of Medicine, Minia University, Minia, Egypt. 2. Pathology and Laboratory Medicine, London Health Sciences Centre, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.
Abstract
BACKGROUND: Vitiligo is a depigmentary skin disfigurement resulting from destruction of melanocytes caused by a possible malfunctioning immunity. This destruction could be linked to an aberrant T-cell-mediated immune response. Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1) are immune checkpoints capable of downregulating T-cell immune functions. OBJECTIVES: To evaluate the pattern of expression of PD-1 and CTLA-4 in active vitiligo skin. METHODS: Thirty nonsegmental vitiligo (NSV) patients had been included in this pilot study. Marginal, lesional, and nonlesional skin biopsies were obtained. PD-1 and CTLA-4 immunohistochemistry expression in the mononuclear inflammatory infiltrates were evaluated using digital images. RESULTS: The marginal and lesional inflammatory infiltrates were significantly abundant when compared to nonlesional ones. The marginal infiltrates were significantly abundant when compared to the lesional ones. PD-1 and CTLA-4 were significantly expressed in the marginal and lesional infiltrates when compared to nonlesional skin. Moreover, the marginal expression of PD-1 was significantly higher than the lesional expression. However, no similar significant difference in CTLA-4 expression was found between the marginal and lesional infiltrates. Significant positive correlations were found between the expressions of PD-1 and CTLA-4 in marginal and lesional infiltrates. CONCLUSION: Programmed death-1 and CTLA-4 are expressed within the inflammatory infiltrate of active NSV. Further studies are required to confirm their significance in the development or limitation of the disease.
BACKGROUND: Vitiligo is a depigmentary skin disfigurement resulting from destruction of melanocytes caused by a possible malfunctioning immunity. This destruction could be linked to an aberrant T-cell-mediated immune response. Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1) are immune checkpoints capable of downregulating T-cell immune functions. OBJECTIVES: To evaluate the pattern of expression of PD-1 and CTLA-4 in active vitiligo skin. METHODS: Thirty nonsegmental vitiligo (NSV) patients had been included in this pilot study. Marginal, lesional, and nonlesional skin biopsies were obtained. PD-1 and CTLA-4 immunohistochemistry expression in the mononuclear inflammatory infiltrates were evaluated using digital images. RESULTS: The marginal and lesional inflammatory infiltrates were significantly abundant when compared to nonlesional ones. The marginal infiltrates were significantly abundant when compared to the lesional ones. PD-1 and CTLA-4 were significantly expressed in the marginal and lesional infiltrates when compared to nonlesional skin. Moreover, the marginal expression of PD-1 was significantly higher than the lesional expression. However, no similar significant difference in CTLA-4 expression was found between the marginal and lesional infiltrates. Significant positive correlations were found between the expressions of PD-1 and CTLA-4 in marginal and lesional infiltrates. CONCLUSION:Programmed death-1 and CTLA-4 are expressed within the inflammatory infiltrate of active NSV. Further studies are required to confirm their significance in the development or limitation of the disease.
Authors: Adam P Curnock; Giovanna Bossi; Jyothi Kumaran; Lindsay J Bawden; Rita Figueiredo; Rajeevkumar Tawar; Katherine Wiseman; Emma Henderson; Sec Julie Hoong; Veronica Gonzalez; Hemza Ghadbane; David Eo Knight; Ronan O'Dwyer; David X Overton; Christina M Lucato; Nicola Mg Smith; Carlos R Reis; Keith Page; Lorraine M Whaley; Michelle L McCully; Stephen Hearty; Tara M Mahon; Peter Weber Journal: JCI Insight Date: 2021-10-22