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Altered systemic and intestinal IgA immune responses in individuals with type 1 diabetes

Huang, Juan, Huang, Gan, Li, Xia, Hu, Fang, Xie, Zhiguo, Xiao, Yang, Luo, Shuoming, Chao, Chen, Guo, Keyu, Wong, F. Susan, Zhou, Zhiguang and Wen, Li 2020. Altered systemic and intestinal IgA immune responses in individuals with type 1 diabetes. Journal of Clinical Endocrinology and Metabolism 105 (12) , dgaa590. 10.1210/clinem/dgaa590

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Oxford University Press
ISSN: 0021-972X
Date of Acceptance: 28 August 2020
Last Modified: 30 Oct 2020 12:30
URI: http://orca.cardiff.ac.uk/id/eprint/136022

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