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- Title
Altered Systemic and Intestinal IgA Immune Responses in Individuals With Type 1 Diabetes.
- Authors
Juan Huang; Gan Huang; Xia Li; Fang Hu; Zhiguo Xie; Yang Xiao; Shuoming Luo; Chen Chao; Keyu Guo; Wong, F. Susan; Zhiguang Zhou; Li Wen; Huang, Juan; Huang, Gan; Li, Xia; Hu, Fang; Xie, Zhiguo; Xiao, Yang; Luo, Shuoming; Chao, Chen
- Abstract
<bold>Objective: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
TYPE 1 diabetes; IMMUNOGLOBULIN A; IMMUNE response; INTESTINAL mucosa; B cells; IMMUNOGLOBULIN producing cells; GUT microbiome; GLUTAMATE decarboxylase
- Publication
Journal of Clinical Endocrinology & Metabolism, 2020, Vol 105, Issue 12, p1
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/clinem/dgaa590