ABSTRACT

Background

T-helper 2 (Th2)-associated cytokines are involved in the pathogenesis of bullous pemphigoid (BP), an autoimmune skin disease. Increased expression of Th2 cytokines such as interleukin-4 (IL-4), IL-5, IL-6, IL-10, and IL-13 have been observed in serum, skin biopsies and/or blister fluid. This study aimed to uncover a possible association between Th2 cytokine genetic variations and susceptibility to BP.

Methods

In a cohort study, blood samples of BP patients and controls were obtained and variations in IL-4 (rs2243250 and rs2070874), IL-4R (rs1805010), IL-5 (rs2069812), IL-6 (rs1800795), IL-10 (rs1800896, rs1800871, and rs1800872), and IL-13 (rs1800925 and rs20541) were genotyped by PCR-RFLP assays. Furthermore, quantitative expression levels of IL-13 gene were evaluated by real-time RT-PCR analysis.

Results

Among the studied variations, a significantly higher frequency of the C-allele was observed in IL-13 gene variation (rs1800925) in the healthy individuals than BP patients. This may indicate a protective effect of C-allele on predisposition to BP. Considering individuals carrying polymorphic genotypes compared to wild genotype, the minor G-allele of IL-4R rs1805010 and A-allele of IL-13 rs20541 had a promotive and protective effect, respectively, on predisposing to the development of BP. No significant difference in IL-13 mRNA expression was detected between BP patients and healthy individuals.

Conclusions

Our results indicate that IL-13 rs1800925 variation may be a protective genetic marker for the development of BP. Given this preventive effect against BP, therapeutic strategies could potentially be developed interfering with the functions of IL-13 cytokine, which seems to be integral in the pathogenesis of eosinophilic inflammatory disorders, such as BP.

中文翻译：

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TH2细胞因子基因多态性与大疱性类天疱疮风险的关系

摘要

背景

T-helper 2 (Th2) 相关细胞因子参与了自身免疫性皮肤病大疱性类天疱疮 (BP) 的发病机制。在血清、皮肤活检和/或水疱液中观察到 Th2 细胞因子如白细胞介素 4 (IL-4)、IL-5、IL-6、IL-10 和 IL-13 的表达增加。本研究旨在揭示 Th2 细胞因子遗传变异与 BP 易感性之间可能存在的关联。

方法

在一项队列研究中，获得了 BP 患者和对照的血液样本，并发现 IL-4（rs2243250 和 rs2070874）、IL-4R（rs1805010）、IL-5（rs2069812）、IL-6（rs1800795）、IL-10 的变化（rs1800896、rs1800871 和 rs1800872）和 IL-13（rs1800925 和 rs20541）通过 PCR-RFLP 测定进行基因分型。此外，通过实时 RT-PCR 分析评估 IL-13 基因的定量表达水平。

结果

在研究的变异中，在健康个体的 IL-13 基因变异（rs1800925）中观察到 C 等位基因的频率明显高于 BP 患者。这可能表明 C 等位基因对 BP 易感性具有保护作用。考虑到与野生基因型相比携带多态基因型的个体，IL-4R rs1805010 的次要 G 等位基因和 IL-13 rs20541 的 A 等位基因分别对诱发 BP 的发展具有促进和保护作用。在 BP 患者和健康个体之间未检测到 IL-13 mRNA 表达的显着差异。

结论

我们的研究结果表明，IL-13 rs1800925 变异可能是 BP 发展的保护性遗传标记。鉴于这种对 BP 的预防作用，治疗策略可能会干扰 IL-13 细胞因子的功能，这似乎是嗜酸性粒细胞炎性疾病（如 BP）发病机制中不可或缺的一部分。