Inoue Naoya, Katsumata Yuka, Watanabe Mikio, Ishido Naoko, Manabe Yu, Watanabe Ayano, Masutani Ryota, Hidaka Yoh, Iwatani Yoshinori
a Department of Biomedical Informatics , Division of Health Sciences, Osaka University Graduate School of Medicine , Osaka , Japan and.
b Laboratory for Clinical Investigation , Osaka University Hospital , Osaka , Japan.
Autoimmunity. 2017 May;50(3):182-191. doi: 10.1080/08916934.2016.1261835. Epub 2016 Dec 26.
Graves' disease (GD) and Hashimoto's disease (HD) are autoimmune thyroid diseases (AITDs). Prognosis of AITDs varies in each patient. Toll-like receptors (TLRs) are pattern-recognition receptors that activate signaling pathways involved in the production of proinflammatory cytokines. UNC93B1 is a transcription factor of TLR7 and TLR9. In this study, we examined the association of TLR expression and TLR and UNC93B1 polymorphisms with the development and prognosis of AITDs. The ratio of intracellular TLR7 (iTLR7) and iTLR9 intensities in B cells was lower in patients with GD in remission than in patients with intractable GD (p = 0.0007). The frequency of G allele of TLR7 rs3853839 G/C polymorphism was significantly higher in male patients with GD and intractable GD than in control subjects (p = 0.0062 and 0.0173, respectively). The frequencies of T allele of TLR9 rs187084 C/T polymorphism and C allele of TLR9 rs352140 C/T polymorphism were significantly higher in patients with intractable GD who had GG genotype of TLR7 rs3853839 polymorphism, which is associated with higher TLR7 expression, than in patients with GD in remission (p = 0.0334 and 0.0023, respectively). The frequencies of AA genotype and A allele of UNC93B1 rs308328 polymorphism were significantly higher in patients with GD than in patients with HD (p = 0.0406 and 0.0316, respectively). These results suggested that the ratio of iTLR7 and iTLR9 intensities was associated with the development and intractability of GD and that TLR7 and UNC93B1 polymorphisms were associated with the development of GD.
格雷夫斯病（GD）和桥本氏病（HD）是自身免疫性甲状腺疾病（AITD）。AITD在每个患者中的预后各不相同。Toll样受体（TLR）是激活参与促炎细胞因子产生的信号通路的模式识别受体。UNC93B1是TLR7和TLR9的转录因子。在本研究中，我们研究了TLR表达以及TLR和UNC93B1多态性与AITD的发生发展及预后的关联。与难治性GD患者相比，处于缓解期的GD患者B细胞中细胞内TLR7（iTLR7）和iTLR9强度的比值更低（p = 0.0007）。TLR7 rs3853839 G/C多态性的G等位基因频率在男性GD患者和难治性GD患者中显著高于对照组（分别为p = 0.0062和0.0173）。TLR9 rs187084 C/T多态性的T等位基因频率以及TLR9 rs352140 C/T多态性的C等位基因频率，在具有与较高TLR7表达相关的TLR7 rs3853839多态性GG基因型的难治性GD患者中，显著高于处于缓解期的GD患者（分别为p = 0.0334和0.0023）。UNC93B1 rs308328多态性的AA基因型和A等位基因频率在GD患者中显著高于HD患者（分别为p = 0.
