Evaluation of Pyroptosis-related Indicators in the Pathogenesis of Vitiligo:Across-sectional Comparative Study

Summary

Vitiligo is an acquired pigmentary disorder on skin and/or mucosae, which is characterized by death of melanocytes (MCs), affecting 0.5%-2% of the population worldwide (1). It doesn't affect the health of patients but it has marked social pressure and greatly interfere with their quality of life (2,3). It presents with well circumscribed milky white patches that occur secondary to destruction of melanocyte, it may appear at any age and affect both sexes equally.

It can affect ethnic groups and people of all skin types with no predilection (4).

Clinically, several types of vitiligo are distinguished according to the distribution of the achromic lesions. One or more lesions in a dermatomal pattern are characteristic for segmental vitiligo (SV) while this segmental distribution is absent in non-segmental vitiligo (NSV). The latter variety includes both the focal type and the generalized type (5). Numerous previous studies tried to illustrate the pathogenesis behind the disease, but the exact pathophysiology is still not fully understood. It is a multifactorial disease. Factors include, neural theory, oxidative stress theory, autoimmune hypothesis, intrinsic theory, melanocytorrhagy hypothesis (6). Many theories tried to explain the mechanisms of MC destruction in vitiligo. Apoptosis is one of the most widely studied cell death pathways. In addition, the other two forms of cell death, conventional necrosis and autophagy seem to be involved in the death of vitiligo MCs under certain situations. Moreover, new types of regulated cell death including necroptosis, pyroptosis, and ferroptosis may also participate in the pathogenesis (7). Pyroptosis is a highly inflammatory form of necrosis cell death NCD regulated mainly by caspase-1, which is initiated following large supramolecular complex ermed inflammasome activation (8). The inflammasome-activated Caspases then cleave the pyroptosis-inducing protein Gasdermin D (GSDMD), which forms a pore in the plasma membrane and causes cell lysis as well as the secretion of IL-1β typically (9). Another study suggests that inflammasome activation could be a useful marker for assessing disease progression of vitiligo (10). However, the link between vitiligo and inflammasome activation is still unclear. The inflammasome regulates cell death and inflammation via activation of caspase-1 (11). The activation of caspase-1 promotes the secretion of proinflammatory cytokines IL-1β and IL-18, as well as the initiation of pyroptosis (12). So, evaluation of pyroptosis-related indicators (GASDM-D, IL 1β \& IL-18) may help understanding the obscure inflammasome pathway involvement in the pathogenesis of Vitiligo.

Conditions

• Vitiligo

Interventions

DIAGNOSTIC_TEST

evaluate serum levels pyroptosis-related indicators (GASDM-D, IL 1β & IL-18)

2 ml blood will be collected from all participants (patients and controls) by aseptic venipuncture into plain tubes. Then the samples will be allowed to coagulate during 10-20 minutes. Serum will be obtained by centrifugation at speed of 2000-3000 cycle/min for 20 minutes. Then we collect the supernatant which immediately be frozen at -80°C until analyzed to determine serum levels of pyroptosis-related indicators (GASDM-D, IL 1β \& IL-18). Serum concentration will be assessed by a commercially available double antibody sandwich enzyme-linked immunosorbent assay (ELISA) kit

Sponsors & Collaborators

• Sohag University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2024-02-24

Primary Completion

2024-08-24

Completion

2024-08-24