Biology Department, East Tehran Branch, Islamic Azad University, Tehran, Iran.
Skin Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Mol Genet Genomic Med. 2020 Dec;8(12):e1519. doi: 10.1002/mgg3.1519. Epub 2020 Dec 19.
TH17/IL-23 immune axis is considered to be involved in the pathogenesis of autoimmune and chronic inflammatory diseases. Bullous pemphigoid (BP) is the most frequent autoimmune blistering disease, characterized by the presence of autoantibodies against the components of the dermal-epidermal junction. Animal studies and characterization of patient samples point toward a contribution of TH17 cells in BP pathogenesis. However, genetic polymorphisms in the genes of TH17/IL-23 cytokines have not yet been well investigated in BP.
Detection of polymorphisms in IL-17A (rs2275913 and rs3819025), IL-17F (rs2397084 and rs763780), IL-17RA (rs2229151), and IL-23R (rs2201841, rs7530511, rs11209026, and rs10889677) genes were performed following the collection of blood samples and DNA extraction from BP patients and controls. Gene expression of IL-23R was determined by quantitative RT-PCR analysis.
The prevalence of IL-23R rs7530511 genotypes and alleles, as well as IL-23R rs2201841 alleles, is significantly different between the BP patients and controls. While the minor C-allele of IL-23R rs7530511 is highly present in the patients, the G-allele distribution of IL-23R rs2201841 is significantly more prevalent in the control individuals compared to the BP patients. Genotypes and alleles of other SNPs in IL-17A, IL-17F, and IL-17RA were similarly distributed in patients and controls.
No alteration was found in the gene expression between wild and polymorphic genotypes of IL-23R (rs2201841 and rs7530511) variations, indicating they do not contribute to altering the levels of gene expression in blood. In summary, our data show that the alleles of two SNPs in IL-23R rs2201841 and rs7530511 are associated with BP.
TH17/IL-23 免疫轴被认为与自身免疫和慢性炎症性疾病的发病机制有关。大疱性类天疱疮（BP）是最常见的自身免疫性水疱病，其特征是存在针对表皮-真皮连接成分的自身抗体。动物研究和患者样本的特征表明，TH17 细胞在 BP 发病机制中起作用。然而，TH17/IL-23 细胞因子基因中的遗传多态性尚未在 BP 中得到很好的研究。
在收集 BP 患者和对照的血液样本和 DNA 提取后，对 IL-17A（rs2275913 和 rs3819025）、IL-17F（rs2397084 和 rs763780）、IL-17RA（rs2229151）和 IL-23R（rs2201841、rs7530511、rs11209026 和 rs10889677）基因的多态性进行检测。通过定量 RT-PCR 分析确定 IL-23R 的基因表达。
BP 患者和对照组之间，IL-23R rs7530511 基因型和等位基因以及 IL-23R rs2201841 等位基因的发生率存在显著差异。IL-23R rs7530511 的 minor C-allele 在患者中高度存在，而 IL-23R rs2201841 的 G-allele 分布在对照组中明显高于 BP 患者。IL-17A、IL-17F 和 IL-17RA 中的其他 SNP 的基因型和等位基因在患者和对照组中分布相似。
在 IL-23R（rs2201841 和 rs7530511）变异的野生型和多态型基因型之间，未发现基因表达的改变，表明它们不会导致血液中基因表达水平的改变。总之，我们的数据表明，IL-23R rs2201841 和 rs7530511 两个 SNP 的等位基因与 BP 相关。
