Altered Systemic and Intestinal IgA Immune Responses in Individuals With Type 1 Diabetes

• Published in: The journal of clinical endocrinology and metabolism 2020-12, Vol.105 (12), p.1-e4625
• Main Authors: Huang, Juan, Huang, Gan, Li, Xia, Hu, Fang, Xie, Zhiguo, Xiao, Yang, Luo, Shuoming, Chao, Chen, Guo, Keyu, Wong, F Susan, Zhou, Zhiguang, Wen, Li
• Format: Article
• Language: English
• Subjects: Adolescent; Analysis; Autoantibodies; Autoimmune diseases; Autoimmunity; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Bacteria; Beta cells; Care and treatment; Case-Control Studies; Child; China; Clinical s; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - metabolism; Enzyme-linked immunosorbent assay; Female; Flow cytometry; Gastrointestinal Microbiome - immunology; Glutamate decarboxylase; Glutamic acid; Health aspects; Homeostasis; Humans; Immune response; Immunity - physiology; Immunoglobulin A; Immunoglobulin A - metabolism; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intestine; Intestines - immunology; Lymphocyte Count; Male; Oral cavity; Physiological aspects; Type 1 diabetes
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgaa590

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.