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.
Section of Endocrinology, Department of Internal Medicine, School of Medicine, Yale University, New Haven, Connecticut, USA.
J Clin Endocrinol Metab. 2020 Dec 1;105(12):e4616-25. doi: 10.1210/clinem/dgaa590.
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.
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.
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.
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.
越来越多的证据表明，免疫球蛋白 A（IgA）通过调节肠道内稳态和随后的宿主免疫，对自身免疫易感性产生关键影响。我们假设 1 型糖尿病患者的 IgA 免疫会发生改变。为了验证我们的假设，我们研究了 1 型糖尿病患者的肠道、口腔和外周 IgA 免疫反应。
我们从诊断为 1 型糖尿病（1 年内和 1 年以上）的患者和健康对照个体中采集粪便、口腔和血液样本。通过放射配体测定法检测血清胰岛自身抗体滴度。通过流式细胞术研究 IgA 结合细菌和 IgA 表达 B 细胞。通过酶联免疫吸附试验测量口腔游离 IgA 水平。通过免疫比浊法测定血清和粪便游离 IgA 浓度。
1 年内被诊断为 1 型糖尿病的个体粪便中 IgA 结合细菌的比例高于健康对照个体。粪便中 IgA 结合细菌的比例与谷氨酸脱羧酶自身抗体滴度呈正相关。此外，与 1 年内被诊断为糖尿病的个体相比，病程较长的个体粪便中 IgA 结合细菌的比例更高。与健康对照个体相比，1 型糖尿病患者血清 IgA 浓度升高。
1 型糖尿病患者表现出改变的 IgA 免疫，特别是粪便中 IgA 结合细菌增加，这可能有助于β细胞自身免疫和疾病的发展，因此，可能被视为 1 型糖尿病治疗的新的治疗靶点。
