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

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 cascad...

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Published in:The Journal of experimental medicine Vol. 210; no. 1; p. 191
Main Authors: Zhang, Qibin, Fillmore, Thomas L, Schepmoes, Athena A, Clauss, Therese R W, Gritsenko, Marina A, Mueller, Patricia W, Rewers, Marian, Atkinson, Mark A, Smith, Richard D, Metz, Thomas O
Format: Journal Article
Language:English
Published: United States 14.01.2013
Subjects:
Amino Acid Sequence
Biomarkers - blood
Blood Proteins - analysis
Case-Control Studies
Chromatography, Liquid - methods
Complement C1 Inactivator Proteins - analysis
Complement C1 Inhibitor Protein
Diabetes Mellitus, Type 1 - blood
Diabetes Mellitus, Type 1 - immunology
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - complications
Humans
Hyperglycemia - blood
Hyperglycemia - etiology
Immunity, Innate
Mass Spectrometry - methods
Molecular Sequence Data
Predictive Value of Tests
Proteomics - methods
Reference Values
Reproducibility of Results
ROC Curve
Sensitivity and Specificity
ISSN:1540-9538, 1540-9538
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Summary: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.
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ISSN:1540-9538
1540-9538
DOI:10.1084/jem.20111843