Proinflammatory Cytokine Gene Polymorphisms in Bullous Pemphigoid

Area of Science:

• Immunogenetics
• Dermatology
• Molecular Biology

Background:

• Bullous pemphigoid (BP) is a rare autoimmune blistering skin disease.
• Altered cytokine expression, including IL-1α, IL-1β, IL-8, and TNF-α, is observed in BP patients and contributes to pathogenesis.
• Genetic polymorphisms in cytokine genes may influence susceptibility to BP.

Purpose of the Study:

• To investigate the association between genetic polymorphisms in IL-1α, IL-1β, IL-8, and TNF-α genes and susceptibility to bullous pemphigoid in an Iranian cohort.
• To evaluate the correlation between gene expression levels and specific polymorphisms.

Main Methods:

• Genotyping of single nucleotide polymorphisms (SNPs) in IL-1α (rs1800587), IL-1β (rs1143627, rs16944, rs1143634), IL-8 (rs4073), and TNF-α (rs1799964, rs1800630, rs1799724, rs361525) in BP patients, healthy controls, and pemphigus vulgaris (PV) patients.
• Quantitative gene expression analysis using RT-PCR.

Main Results:

• A significant difference in IL-8 (rs4073) genotype and allele distribution was found between BP patients and controls, with the A-allele being more prevalent in controls and PV patients.
• IL-8 gene expression levels were significantly higher in BP patients compared to controls.
• An association was found between IL-1α rs1800587 and TNF-α rs361525 polymorphisms and altered gene expression levels in BP patients.

Conclusions:

• The minor allele of the IL-8 SNP (rs4073) may confer a protective role against BP susceptibility in the Iranian population.
• Elevated IL-8 gene expression in BP patients is not directly associated with the studied IL-8 polymorphism.
• Specific polymorphisms in IL-1α and TNF-α are linked to altered gene expression, suggesting a role in BP pathogenesis.