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

Not yet recruiting

• Conditions: Serum Gasdermin D in Vitiligo
• Interventions: Diagnostic Test: gasdermin d

• Registration Number: NCT06584643
• Lead Sponsor: Assiut University

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Status Verified: 2023-11
• Study First Submitted: 2023-12-18
• Study First Submitted QC: 2024-09-03
• Last Update Submitted: 2024-09-03
• Study First Posted: 2024-09-05
• Last Update Posted: 2024-09-05
• Study Start: 2024-11
• Primary Completion: 2025-11
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 84

Inclusion Criteria

• All clinically diagnosed cases of vitiligo (segmental and non-segmental).

Exclusion Criteria

1. patients with inflammatory diseases.
2. patients with autoimmne diseases.
3. patients with neurodegenerative diseases.
4. patients with HIV or COVID19 infection or any other type of infections.
5. patients with systemic diseases as liver diseases or having tumors.
6. patients who received systemic treatment in the last 3 months or topical treatment 1 month prior to the study.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
case group	gasdermin d	For every patient, a full history will be taken recording age, gender, education, residence, special habits, age at onset of vitiligo, duration of vitiligo, stability of vitiligo and family history. A detailed cutaneous examination will be performed including skin phototype, Koebner phenomenon, vitiligo clinical type, leukotrichia, Vitiligo Area Severity Index (VASI) and Vitiligo Disease Activity (VIDA) scores.
healthy control	gasdermin d	age and gender matched healthy volunteers as controls

Primary Outcome Measures

Name	Time	Method
Assessment the serum level of Gasdermin D level in vitiligo patients	basline	estimate the serum level of Gasdermin D level in vitiligo patients and correlate its level with disease activity and various disease parameters.