U.S. Department of Energy

Pacific Northwest National Laboratory

Serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes.

TitleSerum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes.
Publication TypeJournal Article
Year of Publication2013
AuthorsZhang Q, Fillmore TL, Schepmoes AA, Clauss TRW, Gritsenko MA, Mueller PW, Rewers M, Atkinson MA, Smith RD, Metz TO
JournalJ Exp Med
KeywordsAmino Acid Sequence, Biological Markers, Blood Proteins, Case-Control Studies, Chromatography, Liquid, Complement C1 Inactivator Proteins, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Humans, Hyperglycemia, Immunity, Innate, Mass Spectrometry, Molecular Sequence Data, Predictive Value of Tests, Proteomics, Reference Values, Reproducibility of Results, ROC Curve, Sensitivity and Specificity
Abstract

Using global liquid chromatography-mass spectrometry (LC-MS)-based proteomics analyses, we identified 24 serum proteins that were significantly variant between those with type 1 diabetes (T1D) and healthy controls. Functionally, these proteins represent innate immune responses, the activation cascade of complement, inflammatory responses, and blood coagulation. Targeted verification analyses were performed on 52 surrogate peptides representing these proteins, with serum samples from an antibody standardization program cohort of 100 healthy control and 50 type 1 diabetic subjects. 16 peptides were verified as having very good discriminating power, with areas under the receiver operating characteristic curve ≥ 0.8. Further validation with blinded serum samples from an independent cohort (10 healthy control and 10 type 1 diabetics) demonstrated that peptides from platelet basic protein and C1 inhibitor achieved both 100% sensitivity and 100% specificity for classification of samples. The disease specificity of these proteins was assessed using sera from 50 age-matched type 2 diabetic individuals, and a subset of proteins, C1 inhibitor in particular, were exceptionally good discriminators between these two forms of diabetes. The panel of biomarkers distinguishing those with T1D from healthy controls and those with type 2 diabetes suggests that dysregulated innate immune responses may be associated with the development of this disorder.

DOI10.1084/jem.20111843
PubMed ID23277452
PubMed Central IDPMC3549705
Grant ListDK070146 / DK / NIDDK NIH HHS / United States
DK32083 / DK / NIDDK NIH HHS / United States
P30 DK57516 / DK / NIDDK NIH HHS / United States
P41 GM103493 / GM / NIGMS NIH HHS / United States
P41 RR018522 / RR / NCRR NIH HHS / United States
P41GM103493 / GM / NIGMS NIH HHS / United States
P41RR018522 / RR / NCRR NIH HHS / United States
R21 DK070146 / DK / NIDDK NIH HHS / United States
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