暴发性1型糖尿病的免疫学特征探讨

Immunological features of fulminant type 1 diabetes

目的探讨暴发性1型糖尿病患者的免疫学特征及其病因学意义。方法筛选暴发性1型糖尿病患者20例及其年龄、性别匹配的经典1型糖尿病患者40例。采用放射配体法检测谷氨酸脱羧酶抗体（GADA）、蛋白酪氨酸磷酸酶抗体（IA2A）和锌转运蛋白8抗体（ZnT8A）；酶联免疫斑点法检测GAD反应性T细胞；直接测序法检测人类白细胞相关抗原（HIJA）DQ基因型。结果本组暴发性1型糖尿病患者8／20胰岛自身抗体阳性，其中7例GADA阳性，4例ZnT8A阳性，3例为GADA与ZnT8均阳性。3例起病初期GADA阳性者，于2年及3年后复查抗体转阴各1例，另1例3年后复查抗体滴度增高（0．34～1．46）。在6例暴发性1型糖尿病患者中3例有GAD反应性T细胞。暴发性1型糖尿病患者HLA—DQA1＊0102-DQB1＊0601和DQA1＊03-DQB1＊0401单体型频率较经典1型患者增高（P=0．005，P=0．035）。结论部分暴发性1型糖尿病患者存在体液或细胞免疫反应及HLA-DQ易感基因型，提示自身免疫反应可能参与暴发性1型糖尿病的发病过程。

Objective To investigate the immunological features of fulminant type 1 diabetes. Methods Twenty patients with fulmlnant type 1 diabetes （F1D） were recruited based upon the criteria proposed by Hanafusa, and 40 patients with classical type 1 diabetes were matched with age, gender and duration for comparison. GADA, IA2A and ZnTSA were determined with radioligand assay, and GAD- reactive T cells were measured by enzyme-linked immunospot（ELISPOT） assay. The HLA-DQ were analyzed by sequence-based genotyping （SBT）. Results Eight of 20 patients with F1D were antobody-positive, including 7 GADA positive,4 ZnTSA positive, and 3 both GADA and ZnT8A positive. The index of 3 GADA positive patients were less than 0. 4 at first visit, two turned to be negative by two or three years. While the GADA index of the patient was 0. 343 at onset and increased to 1. 467 three years later. Among subjects with F1D（3/6） and classical type 1 diabetes （3/6）, were recorded significant GAD-stimulated responses by ELISPOT assay. The frequencies of HLA-DQAI ＊ 0102-DQB1 ＊ 0601 and DQA1 ＊ 03-DQB1 ＊ 0401 were significantly higher in F1D than those in classical type 1 diabetes （ P = 0. 005, P = 0. 035, respectively）. Conclusion Humoral and cellular immunoreactivity and susceptible HLA-DQ genotype exsisted in part of F1D patients, indicating autoimmunity may involve in the pathogenesis of F1D.