Department of Immunobiology, King's College London, London, UK.
School of Clinical Sciences, University of Bristol, Bristol, UK.
Diabet Med. 2022 Sep;39(9):e14860. doi: 10.1111/dme.14860. Epub 2022 May 9.
In the current study we aimed to evaluat T cell phenotypes and metabolic profiles in high-risk individuals who progressed to type 1 diabetes compared to those remaining disease free.
A Fluorspot assay was used to examine T cell responses to a panel of islet autoantigen peptides in samples obtained 6- and 30-months preceding disease onset and at the same timepoints in non-progressors.
We noted a significant increase in the magnitude of the proinflammatory interferon-γ response to proinsulin and insulin peptides in individuals who progressed to type 1 diabetes. In contrast, in the non-progressors, we observed an increase in the regulatory IL-10 response to proinsulin peptides. Furthermore, the T cell responses to the islet peptide panel predisposed towards a proinflammatory interferon-γ bias in the progressors.
Collectively, these data suggest that a proinflammatory T cell response is prevalent in high-risk individuals who progress to type 1 diabetes and can be detected up to 6 months prior to onset of disease. This observation, albeit in a small cohort, can potentially be harnessed in disease staging, particularly in identifying autoantibody-positive individuals transitioning from stage 2 (dysglycemia present and pre-symptomatic) to stage 3 (dysglycemia present and symptomatic). The detection of these different T cell phenotypes in progressors and non-progressors suggests the presence of disease endotypes.
本研究旨在评估与无疾病进展者相比，进展为 1 型糖尿病的高危个体的 T 细胞表型和代谢特征。
使用 Fluorspot assay 检测在疾病发病前 6 个月和 30 个月以及非进展者同期获得的样本中，T 细胞对胰岛自身抗原肽的反应。
我们注意到，在进展为 1 型糖尿病的个体中，对前胰岛素和胰岛素肽的促炎干扰素-γ反应幅度显著增加。相比之下，在非进展者中，我们观察到前胰岛素肽的调节性 IL-10 反应增加。此外，胰岛肽组的 T 细胞反应倾向于进展者的促炎干扰素-γ偏向。
总之，这些数据表明，进展为 1 型糖尿病的高危个体中存在促炎 T 细胞反应，并且可以在疾病发病前 6 个月检测到。尽管在一个小队列中观察到这种情况，但它可能在疾病分期中得到利用，特别是在识别从第 2 阶段（存在血糖异常和无症状）向第 3 阶段（存在血糖异常和有症状）过渡的自身抗体阳性个体。在进展者和非进展者中检测到这些不同的 T 细胞表型提示存在疾病终末类型。
