Department of Endocrinology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
University Institute of Pharmaceutical Sciences (UIPS), Chandigarh, India.
Indian J Med Res. 2017 Jun;145(6):767-776. doi: 10.4103/ijmr.IJMR_1563_15.
BACKGROUND & OBJECTIVES: Type-1 diabetes mellitus (T1DM) and latent autoimmune diabetes in adults (LADA) share similar pathological features but differ in age of onset and progression. There is a scarcity of information on differences in CD4+ T-cell responses, particularly, cytokine secretion, between the two forms of autoimmune diabetes. Here proliferative potential and concentration of pro- and anti-inflammatory cytokines secreted by peripheral blood mononuclear cells (PBMCs) of T1DM and LADA patients were compared, after in vitro stimulation with β-cell autoantigens.
A total of 19 patients with LADA, 37 with T1DM and 20 healthy controls were compared on the basis of lymphocyte proliferation and secretion of pro- and anti-inflammatory cytokines belonging to different T-helper types after in vitro stimulation of PBMCs with insulin and glutamic acid decarboxylase 65 (GAD65).
Following insulin stimulation, LADA group secreted higher concentration of interleukin-17 (IL-17) (P=0.02) and had higher proportion of interferon gamma (IFN-γ) secretors (P<0.001) than T1DM group. Post-GAD65 stimulation, higher proportion of LADA patients secreted IL-23 than T1DM group (P=0.02). Proportion of responders , as well as levels of secreted IL-10, were significantly higher in LADA than T1DM group, following stimulation with both insulin (P=0.01) and GAD65 (P=0.03). A significant positive correlation was observed between body mass index and IL-17 levels (r=0.41, P=0.04) and fasting plasma C-peptide with IL-10 levels (r=0.37, P=0.04).
INTERPRETATION & CONCLUSIONS: There are differences in the portfolio of cytokine secretion in diabetic subjects with varying rates of β-cell destruction as LADA subjects secrete higher levels of both pro- and anti-inflammatory cytokines on exposure to β-cell autoantigens, thus highlighting another distinguishing feature in the pathophysiology of the two forms of autoimmune diabetes.
1 型糖尿病（T1DM）和成人隐匿性自身免疫糖尿病（LADA）具有相似的病理特征，但发病年龄和进展程度不同。关于这两种自身免疫性糖尿病之间 CD4+T 细胞反应（尤其是细胞因子分泌）的差异信息较少。在此，我们比较了 T1DM 和 LADA 患者外周血单个核细胞（PBMC）在体外经胰岛自身抗原刺激后的增殖潜力和促炎及抗炎细胞因子的浓度。
根据 PBMC 经胰岛素和谷氨酸脱羧酶 65（GAD65）体外刺激后产生的淋巴细胞增殖和促炎及抗炎细胞因子的分泌情况，比较了 19 例 LADA 患者、37 例 T1DM 患者和 20 例健康对照者之间的差异。
经胰岛素刺激后，LADA 组分泌的白细胞介素-17（IL-17）浓度较高（P=0.02），干扰素-γ（IFN-γ）分泌者的比例较高（P<0.001）。经 GAD65 刺激后，LADA 组分泌 IL-23 的患者比例高于 T1DM 组（P=0.02）。与 T1DM 组相比，LADA 组经胰岛素（P=0.01）和 GAD65（P=0.03）刺激后，应答者比例及分泌的 IL-10 水平均显著升高。IL-17 水平与体重指数呈正相关（r=0.41，P=0.04），空腹血浆 C 肽与 IL-10 水平呈正相关（r=0.37，P=0.04）。
由于 LADA 患者在接触胰岛自身抗原时会分泌更高水平的促炎和抗炎细胞因子，因此在具有不同β细胞破坏速度的糖尿病患者中，细胞因子分泌谱存在差异，这突出了两种自身免疫性糖尿病在病理生理学上的另一个区别特征。
