Liu Xi-Yu, Li Hong
Department of Endocrinology, Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang, China.
Department of Endocrinology, Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang, China; Department of Endocrinology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
J Diabetes Res. 2017;2017:8365762. doi: 10.1155/2017/8365762. Epub 2017 Mar 15.
. Latent autoimmune diabetes in adults (LADA) is an autoimmune disease of which the mechanism is not clear. Emerging evidence suggests that histone methylation contributes to autoimmunity. . Blood CD4 T lymphocytes from 26 LADA patients and 26 healthy controls were isolated to detect histone H3 lysine 4 and H3 lysine 9 methylation status. . Reduced global H3 lysine 9 methylation was observed in LADA patients' CD4 T lymphocytes, compared to healthy controls ( < 0.05). H3 lysine 4 methylation was not statistically different. The reduced H3 lysine 9 methylation was associated with GADA titer but not correlated with glycosylated hemoglobin (HbA1c). When the LADA patient group was divided into those with complication and those without, relatively reduced global H3 lysine 9 methylation was observed in LADA patients with complication ( < 0.05). The expression of histone methyltransferase SUV39H2 for H3 lysine 9 methylation was downregulated in LADA patients, and the expression of histone demethylase KDM4C which made H3 lysine 9 demethylation was upregulated. . The reduction of histone H3 lysine 9 methylation which may due to the downregulation of methyltransferase SUV39H2 and the upregulation of demethylase KDM4C was found in CD4 T lymphocytes of LADA patients.
成人隐匿性自身免疫糖尿病（LADA）是一种发病机制尚不明确的自身免疫性疾病。新出现的证据表明，组蛋白甲基化与自身免疫有关。从26例LADA患者和26例健康对照者中分离出血液CD4 T淋巴细胞，检测组蛋白H3赖氨酸4和H3赖氨酸9的甲基化状态。与健康对照者相比，LADA患者的CD4 T淋巴细胞中整体H3赖氨酸9甲基化水平降低（P<0.05）。H3赖氨酸4甲基化无统计学差异。H3赖氨酸9甲基化水平降低与谷氨酸脱羧酶自身抗体（GADA）滴度相关，但与糖化血红蛋白（HbA1c）无关。将LADA患者组分为有并发症组和无并发症组，有并发症的LADA患者中整体H3赖氨酸9甲基化水平相对降低（P<0.05）。LADA患者中负责H3赖氨酸9甲基化的组蛋白甲基转移酶SUV39H2表达下调，而导致H3赖氨酸9去甲基化的组蛋白去甲基酶KDM4C表达上调。在LADA患者的CD4 T淋巴细胞中发现，可能由于甲基转移酶SUV39H2下调和去甲基酶KDM4C上调导致组蛋白H3赖氨酸9甲基化水平降低。
