Clinical manifestation and islet β-cell function of a subtype of latent autoimmune diabetes in adults (LADA): positive for T cell responses in phenotypic type 2 diabetes
Clinical manifestation and islet β-cell function of a subtype of latent autoimmune diabetes in adults (LADA): positive for T cell responses in phenotypic type 2 diabetes
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DOI：
10.1007/s00592-019-01391-w
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发表时间：
2019-11-01
影响因子：
3.8
通讯作者：
Zhou, Zhiguang
中科院分区：
文献类型：
--
作者：
Liang, Huiying;Cheng, Ying;Zhou, Zhiguang
目的探讨通过酶联免疫斑点（ELISPOT）从表型2型糖尿病（T2 D）患者中识别成人潜伏性自身免疫糖尿病（LADA）亚型T-LADA（T细胞反应阳性且自身抗体阴性）的可能性。方法对82例表型T2 D患者进行研究。用放射配体法检测谷氨酸脱羧酶（GAD）、胰岛素瘤相关蛋白2和锌转运蛋白8的自身抗体。39例Ab（+）和43例Ab（-）表型T2 D患者入组，通过ELISPOT检测对GAD 65和C肽抗原的T细胞应答。结果（1）ELISPOT检测43例Ab（-）表型T2 D患者中11例显示IFN-γ分泌性T细胞，而39例Ab（+）表型T2 D患者中13例显示胰岛抗原T细胞反应阳性。(2)表型T2 D T细胞（+）患者的发病年龄比T细胞（-）患者的发病年龄小（42.7 +/- 9.3 vs. 48.2 +/- 10.2岁，P = 0.025）。此外，与T细胞（-）参与者相比，T细胞（+）T2 D患者的空腹C肽（FCP）显著降低[0.28（0.02-0.84）vs. 0.42（0.05-1.26）nmol/L，P = 0.013]。(3)Ab（-）T（+）组FCP显著低于Ab（-）T（-）组[0.31（0.13-0.84）vs. 0.51（0.07-1.26）nmol/L，P = 0.023]。结论通过检测表型T2 D患者的T细胞对胰岛抗原的反应，我们确定了LADA的一种特殊亚型，其可能与比经典T2 D更差的基础β细胞功能相关（Ab（-）T（-））。
Aims To investigate the possibility of identifying a subtype of latent autoimmune diabetes in adults (LADA), T-LADA (T cell responses-positive and autoantibody-negative) from patients with phenotypic type 2 diabetes (T2D) by enzyme-linked immunospot (ELISPOT). Methods Eighty-two patients with phenotypic T2D were studied. Autoantibodies against glutamic acid decarboxylase (GAD), insulinoma-associated protein-2 and zinc transporter 8 were measured by radioligand assay. Thirty-nine Ab(+) and 43 Ab(-) patients with phenotypic T2D were enrolled for T cell assay of responses to GAD65 and C-peptide antigen by ELISPOT. Results (1) Eleven of 43 Ab(-) participants with phenotypic T2D were demonstrated interferon (IFN)-gamma secreting T cells by ELISPOT, while 13 of 39 Ab(+) patients with phenotypic T2D were positive for T cells responses to islet antigens. (2) The onset ages of T cell(+) people with phenotypic T2D were younger than that of T cell(-) individuals (42.7 +/- 9.3 vs. 48.2 +/- 10.2 years, P = 0.025). Moreover, T cell(+) patients with T2D displayed a significantly lower fasting C-peptide (FCP) compared with T cell(-) participants [0.28 (0.02-0.84) vs. 0.42 (0.05-1.26) nmol/L, P = 0.013]. (3) Ab(-)T(+) group had a significantly lower FCP compared with Ab(-)T(-) group [0.31 (0.13-0.84) vs. 0.51 (0.07-1.26) nmol/L, P = 0.023]. Conclusions By measuring T cell responses to islet antigens in patients with phenotypic T2D, we identified a specific subtype of LADA who may be associated with worse basal beta-cell function than classic T2D (Ab(-)T(-)).