The pathophysiology underlying the autoimmune disease type 1 diabetes (T1D) is poorly understood. Obtaining an accurate proteomic profile of the T helper cell population is essential for understanding the pathogenesis of T1D. Here, we performed in-depth proteomic profiling of peripheral CD4+ T cells in a pediatric cohort to identify cellular signatures associated with the onset of T1D. Using only 250 000 CD4+ T cells per patient, isolated from biobanked PBMC samples, we identified nearly 6000 proteins using deep-proteome profiling with LC–MS/MS data-independent acquisition. Our analysis revealed an inflammatory signature in patients with T1D; this signature is characterized by circulating mediators of neutrophils, platelets, and the complement system. This signature likely reflects the inflammatory extracellular milieu, which suggests that activation of the innate immune system plays an important role in disease onset. Our results emphasize the potential value of using high-resolution LC–MS/MS to investigate limited quantities of biobanked samples to identify disease-relevant proteomic patterns. Proteomic profiles of 114 individuals have been deposited in a comprehensive portable repository serving as a unique resource for CD4+ T cell expression in the context of both health and T1D disease.

中文翻译：

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在最近发病的1型糖尿病患者中CD4 + T细胞的蛋白质组学景观。

对自身免疫性1型糖尿病（T1D）的病理生理了解甚少。获得T辅助细胞群的准确蛋白质组学特征对于理解T1D的发病机理至关重要。在这里，我们对儿童队列中的外周CD4 + T细胞进行了深入的蛋白质组分析，以鉴定与T1D发作相关的细胞标志。从每位患者中仅250000个CD4 + T细胞（从生物库PBMC样本中分离），我们使用具有LC-MS / MS数据独立采集的深层蛋白质组分析技术鉴定了近6000种蛋白质。我们的分析显示，T1D患者有炎症反应。该特征的特征在于中性粒细胞，血小板和补体系统的循环介质。这个特征可能反映出炎性的细胞外环境，这表明先天免疫系统的激活在疾病发作中起重要作用。我们的结果强调了使用高分辨率LC-MS / MS研究有限数量的生物库样品以鉴定与疾病相关的蛋白质组学模式的潜在价值。在健康和T1D疾病的背景下，已将114个个体的蛋白质组学概况存储在一个全面的便携式存储库中，作为CD4 + T细胞表达的独特资源。