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Lepper, M.F. ; Ohmayer, U. ; von Toerne, C. ; Maison, N. ; Ziegler, A.-G. ; Hauck, S.M.

Proteomic landscape of patient-derived CD4+T cells in recent-onset type 1 diabetes.

J. Proteome Res. 17, 618-634 (2017)
Postprint DOI PMC
Open Access Green
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Type 1 Diabetes ; Cd4+t Cells ; Proteomic Profiling ; Lc-ms/ms ; Data-independent Acquisition ; Meta-human Spectral Library ; Autoimmune ; Inflammation ; Biomarker ; Neutrophil; Combined Transmembrane Topology; Neutrophil Extracellular Traps; Data-independent Acquisition; Signal Peptide Prediction; Gene-expression; Peripheral-blood; T-cells; Children; Autoimmunity; Risk
ISSN (print) / ISBN 1535-3893
e-ISSN 1535-3907
Journal Journal of Proteome Research
Quellenangaben Volume: 17, Issue: 1, Pages: 618-634 Article Number: , Supplement: ,
Publisher American Chemical Society (ACS)
Publishing Place Washington
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CF Metabolomics & Proteomics (CF-MPC)
Institute of Asthma and Allergy Prevention (IAP)
Institute of Diabetes Research Type 1 (IDF)