Arakawa Y, Watanabe M, Takemura K, Inoue N, Hidaka Y, Iwatani Y
Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Department of Laboratory Medicine, Osaka University Hospital, Suita, Osaka, Japan.
Int J Immunogenet. 2017 Apr;44(2):41-50. doi: 10.1111/iji.12305. Epub 2017 Feb 5.
To clarify the association between the genetic producibility of IL-15, a pro-inflammatory cytokine, and the pathogenesis of autoimmune thyroid diseases (AITDs), we genotyped +96522 A>T and +82889 A>G polymorphisms in the IL15 gene using 127 patients with Hashimoto's disease (HD), including 55 patients with severe HD and 48 patients with mild HD; 130 patients with Graves' disease (GD), including 52 patients with intractable GD and 44 patients with GD in remission; and 79 healthy volunteers. Both the IL15 +96522 A allele and AA genotype were more frequent in patients with severe HD than in those with mild HD. The serum levels of IL-15 were higher in individuals with the IL15 +96522 AA genotype than in those with the T allele, and they were also higher in patients with severe HD than in those with mild HD. On the other hand, the mRNA levels of IL-15 were not significantly different among individuals with each genotype of both SNPs. After incubation with recombinant human IL-15, the proportions of Th17 cells in CD4 cells were increased, and those of Treg cells in CD4 cells were maintained. Our study indicates that the IL15 +96522A/C polymorphism correlates with the severity of HD, most likely by increasing Th17 cells.
为了阐明促炎细胞因子白细胞介素-15（IL-15）的基因可表达性与自身免疫性甲状腺疾病（AITD）发病机制之间的关联，我们对127例桥本氏病（HD）患者、130例格雷夫斯病（GD）患者和79名健康志愿者的IL15基因中的+96522 A>T和+82889 A>G多态性进行了基因分型。其中，127例HD患者包括55例重度HD患者和48例轻度HD患者；130例GD患者包括52例难治性GD患者和44例缓解期GD患者。重度HD患者中IL15 +96522 A等位基因和AA基因型的频率高于轻度HD患者。IL15 +96522 AA基因型个体的血清IL-15水平高于T等位基因个体，重度HD患者的血清IL-15水平也高于轻度HD患者。另一方面，两种单核苷酸多态性（SNP）各基因型个体之间的IL-15 mRNA水平无显著差异。用重组人IL-15孵育后，CD4细胞中Th17细胞的比例增加，CD4细胞中调节性T细胞（Treg）的比例保持不变。我们的研究表明，IL15 +96522A/C多态性与HD的严重程度相关，很可能是通过增加Th17细胞实现的。
