B7H3 和 B7H4 基因多态性及其蛋白表达与自身免疫性甲状腺疾病的发生发展及预后的关系。
Association of B7H3 and B7H4 gene polymorphisms and protein expression with the development and prognosis of autoimmune thyroid diseases.
机构信息
Division of Health Sciences, Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Osaka, Japan.
Laboratory for Clinical Investigation, Osaka University Hospital, Osaka, Japan.
出版信息
Clin Endocrinol (Oxf). 2023 Jul;99(1):103-112. doi: 10.1111/cen.14923. Epub 2023 Apr 26.
BACKGROUND
The prognosis of autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and Hashimoto's disease (HD), varies among patients. B7-H3 and B7-H4, members of the B7 family of proteins, regulate immune response. To clarify the association of B7-H3 and B7-H4 with the pathogenesis and prognosis of AITDs, we examined the expression of the soluble and membrane form of B7-H3 and B7-H4 and genotyped single nucleotide polymorphisms (SNPs) in the B7H3 and B7H4 genes.
METHODS
We examined the expression of the membrane form of B7-H3 and B7-H4 by flow cytometry and their soluble forms by enzyme-linked immunosorbent assay. We genotyped SNPs in B7H3 and B7H4 in 187 GD patients, 217 HD patients, and 110 healthy volunteers using the PCR-RFLP method.
RESULTS
The frequency of the B7H3 rs3816661 CC genotype was higher in patients with severe HD. G carriers of B7H4 rs10754339 A/G and B7H4 rs13505 T/G were more frequent in patients with AITD. A carrier of B7H4 rs10158166 A/G and C carriers of B7H4 rs3806373 C/T were more frequent in patients with intractable GD. The proportion of B7-H3 monocytes was higher in the CC genotype of B7H3 rs3816661 C/T than in the other genotypes and was lower in patients with GD and HD than in healthy controls. The concentration of soluble B7-H4 was lower in the TG genotype of B7H4 rs13505 T/G than in the TT genotype and was higher in patients with AITD than in healthy controls.
CONCLUSION
B7H3 and B7H4 are associated with AITD susceptibility and prognosis.
背景
自身免疫性甲状腺疾病（AITD）的预后各不相同，包括格雷夫斯病（GD）和桥本甲状腺炎（HD）。B7-H3 和 B7-H4 是 B7 蛋白家族的成员，调节免疫反应。为了阐明 B7-H3 和 B7-H4 与 AITD 发病机制和预后的关系，我们检测了可溶性和膜结合形式的 B7-H3 和 B7-H4 的表达，并对 B7H3 和 B7H4 基因的单核苷酸多态性（SNP）进行了基因分型。
方法
我们通过流式细胞术检测 B7-H3 和 B7-H4 的膜结合形式，通过酶联免疫吸附试验检测其可溶性形式。我们采用 PCR-RFLP 法对 187 例 GD 患者、217 例 HD 患者和 110 名健康志愿者的 B7H3 和 B7H4 基因中的 SNP 进行基因分型。
结果
B7H3 rs3816661 CC 基因型在重度 HD 患者中的频率较高。B7H4 rs10754339 A/G 和 B7H4 rs13505 T/G 的 G 携带者在 AITD 患者中更为常见。B7H4 rs10158166 A 携带者和 B7H4 rs3806373 C/T 的 C 携带者在难治性 GD 患者中更为常见。B7H3 单核细胞中 B7H3 rs3816661 C/T 的 CC 基因型比例高于其他基因型，GD 和 HD 患者低于健康对照组。B7H4 rs13505 T/G 的 TG 基因型可溶性 B7-H4 浓度低于 TT 基因型，AITD 患者高于健康对照组。
结论
B7H3 和 B7H4 与 AITD 的易感性和预后相关。
Zotero 插件