Juan Huang1,2, Gan Huang1, Xia Li1, Fang Hu1, Zhiguo Xie1, Yang Xiao1, Shuoming Luo1, Chen Chao1, Keyu Guo1, F Susan Wong3, Zhiguang Zhou1, Li Wen2. 1. National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education; and Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. 2. Section of Endocrinology, Department of Internal Medicine, School of Medicine, Yale University, New Haven, Connecticut, USA. 3. Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, Wales, UK.
Abstract
OBJECTIVE: Increasing evidence supports the observation that immunoglobulin A (IgA) exerts a critical effect on the susceptibility to autoimmunity by modulating gut homeostasis and subsequent host immunity. We hypothesized that the IgA immunity is altered in individuals with type 1 diabetes. To test our hypothesis, we investigated intestinal, oral, and peripheral IgA immune responses in individuals with type 1 diabetes. METHODS: We collected stool, oral cavity, and blood samples from participants diagnosed with type 1 diabetes (within 1 year and more than 1 year) and healthy control individuals. Serum islet autoantibody titers were detected by radioligand assays. IgA-bound bacteria and IgA-expressing B cells were studied by flow cytometry. Oral free IgA level was measured by enzyme-linked immunosorbent assay. Serum and stool free IgA concentrations were determined by immune-turbidimetry method. RESULTS: Individuals diagnosed with type 1 diabetes within 1 year had an increased proportion of stool IgA-bound bacteria compared with healthy control individuals. The proportion of stool IgA-bound bacteria was positively associated with glutamic acid decarboxylase autoantibody titer. Moreover, individuals with a longer disease duration displayed a higher level of IgA-bound bacteria than those diagnosed within 1 year. In contrast to healthy control individuals, type 1 diabetes patients had increased serum IgA concentrations. CONCLUSIONS: Individuals with type 1 diabetes display altered IgA immunity, especially increased stool IgA-bound bacteria, which is likely to contribute to β-cell autoimmunity and the disease development, and thus, might be considered as a novel therapeutic target for the treatment of type 1 diabetes.
OBJECTIVE: Increasing evidence supports the observation that immunoglobulin A (IgA) exerts a critical effect on the susceptibility to autoimmunity by modulating gut homeostasis and subsequent host immunity. We hypothesized that the IgA immunity is altered in individuals with type 1 diabetes. To test our hypothesis, we investigated intestinal, oral, and peripheral IgA immune responses in individuals with type 1 diabetes. METHODS: We collected stool, oral cavity, and blood samples from participants diagnosed with type 1 diabetes (within 1 year and more than 1 year) and healthy control individuals. Serum islet autoantibody titers were detected by radioligand assays. IgA-bound bacteria and IgA-expressing B cells were studied by flow cytometry. Oral free IgA level was measured by enzyme-linked immunosorbent assay. Serum and stool free IgA concentrations were determined by immune-turbidimetry method. RESULTS: Individuals diagnosed with type 1 diabetes within 1 year had an increased proportion of stool IgA-bound bacteria compared with healthy control individuals. The proportion of stool IgA-bound bacteria was positively associated with glutamic acid decarboxylase autoantibody titer. Moreover, individuals with a longer disease duration displayed a higher level of IgA-bound bacteria than those diagnosed within 1 year. In contrast to healthy control individuals, type 1 diabetes patients had increased serum IgA concentrations. CONCLUSIONS: Individuals with type 1 diabetes display altered IgA immunity, especially increased stool IgA-bound bacteria, which is likely to contribute to β-cell autoimmunity and the disease development, and thus, might be considered as a novel therapeutic target for the treatment of type 1 diabetes.
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