Evaluation of Serum Gasdermin D Level As a Potential Biomarker of Disease Activity in Vitiligo Patients

Overview

Assessment the serum level of Gasdermin D level in vitiligo patients. Correlate its level with disease activity scores using Vitiligo Area Severity Index (VASI) and Vitiligo Disease Activity (VIDA) scores and with different disease parameters.

Vitiligo, a common depigmenting skin disorder, has an estimated prevalence of 0.5-2% of the population worldwide. The disease is characterized by the selective loss of melanocytes which results in typical nonscaly, chalky-white macules. In recent years, considerable progress has been made in our understanding of the pathogenesis of vitiligo which is now clearly classified as an autoimmune disease . The destruction of melanocyte is thought to be of multifactorial causation. Genome-wide associated studies have identified single-nucleotide polymorphisms in a panel of susceptible loci as risk factors in melanocyte death. But vitiligo onset can't be solely attributed to a susceptive genetic background . Oxidative stress triggered by elevated levels of reactive oxygen species accounts for melanocytic molecular and organelle dysfunction, in addition to the self-responsive immune function directly contributes to the bulk of melanocyte deaths in vitiligo . Moreover, apoptosis is the most extensively documented way of melanocyte demise, with few melanocytes undergo necrosis. But forms of cell death are not merely restricted to apoptosis and necrosis. Cells may die from accidental cell death (ACD) or regulated cell death (RCD). ACD, like necrosis, is biologically uncontrolled, whereas RCD (apoptosis, necroptosis, pyroptosis, oxeiptosis, ferroptosis, parthanatos, etc.) involves precise signaling cascade and molecular mechanisms . Pyroptosis is mechanistically distinct from other forms of cell death with gasdermin D (GSDMD) and caspase-1/4/5/11 activation as its defining feature . Upon being stimulated by damage-associated molecular patterns molecules (DAMPs), pathogen-associated molecular patterns molecules or altered homeostasis, caspases are activated to cleave the downstream GSDMD. GSDMD fragment with membrane pore-forming activity yields plasma membrane rupture, cytosolic content release, and concurrent cell swelling and lysis Gasdermins belong to the pore-forming protein family and consist of six gasdermin proteins, including gasdermins A-E. The members of the gasdermin family have two domains: an N-terminal domain and a C-terminal domain linked by a flexible peptide. Upon activation, the cleaved N-terminal domain is responsible for inducing pyroptosis . GSDMD, the most extensively studied executive pyroptosis-executing protein with the clearest mechanism. In a previous study, scRNA-seq datasets of skin-derived cells from healthy donors and patients with vitiligo were analysed. Results demonstrated that CASP1, CASP4, CASP6, CASP8, and GSDMD expression was significantly upregulated in melanocytes of patients with vitiligo. These results indicated that pyroptosis signaling is an important pathway in the development of vitiligo . To the best of our knowledge, no previous studies have evaluated the serum level of Gasdermin D as a potential biomarker in vitiligo patients.

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