The proteomic landscape of patient-derived CD4+ T cells in recent-onset type 1 diabetes

ABSTRACT: 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 in order 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 6,000 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, suggesting 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 in order to identify disease-relevant proteomic patterns. The deposited data set is the shotgun proteomic part of our two-phase study.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cd4-positive Helper T Cell, Helper T-lymphocyte

DISEASE(S): Type 1 Diabetes Mellitus

SUBMITTER: Marlen Lepper  

LAB HEAD: Stefanie M. Hauck

PROVIDER: PXD006223 | Pride | 2017-11-30

REPOSITORIES: Pride