Open AccessDecreased mi R ‐146 expression in peripheral blood mononuclear cells is correlated with ongoing islet autoimmunity in type 1 diabetes patients 1型糖尿病患者外周血单个核细胞miR‐146表达下调与胰岛持续免疫失衡相关
Author(s) -
Yang Minglan,
Ye Lei,
Wang Bokai,
Gao Jie,
Liu Ruixin,
Hong Jie,
Wang Weiqing,
Gu Weiqiong,
Ning Guang
Publication year - 2015
Publication title -
journal of diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.949
H-Index - 43
eISSN - 1753-0407
pISSN - 1753-0393
DOI - 10.1111/1753-0407.12163
Subject(s) - medicine , peripheral blood mononuclear cell , autoimmunity , downregulation and upregulation , autoantibody , immunology , endocrinology , glutamate decarboxylase , pathogenesis , diabetes mellitus , autoimmune disease , antibody , gene , biology , biochemistry , in vitro , enzyme
Background Type 1 diabetes mellitus ( T1D ) is a common autoimmune disease mediated by autoimmune attack against pancreatic β‐cells. It has been reported that dysregulation of micro RNA s ( miRNA s) may contribute to the pathogenesis of autoimmune diseases, including T1D . The aim of the present study was to identify pathogenic miRNA s in peripheral blood mononuclear cells ( PBMC ) of T1D patients. Methods Global miRNA and mRNA expression was profiled in PBMC from 12 patients with newly diagnosed T1D and 10 normal controls. Differently expressed miRNA s were validated in an independent set of patients and controls. The dynamic changes in miRNA and target gene expression were analyzed in T1D patients treated with either a short (6 months) or long (12–24 months) course of insulin. The association between miRNA expression and serum glutamic acid decarboxylase antibody ( GADA ) titers was also investigated. Results Compared with normal controls, there were 26 miRNAs and 1218 genes differently expressed in PBMC of patients with newly diagnosed T1D . The greatest downregulation was for mi R ‐146a (48% decrease; P < 0.05). Expression of its target genes, predicted to be tumor necrosis factor receptor‐associated factor 6 ( TRAF6 ), B cell CLL /lymphoma 11A ( BCL11A ), syntaxin 3 ( STX3 ) and numb homolog ( NUMB ), was upregulated. Moreover, T1D patients on long‐course insulin and optimized glucose control had sustained low expression of mi R ‐146. Interestingly, decreased mi R ‐146a expression was significantly associated with high serum GADA titers ( P < 0.05). Conclusions The results suggest that dysregulation of mi R ‐146 expression in PBMC may be associated with the ongoing autoimmune imbalance in T1D patients.