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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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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549705/
https://www.ncbi.nlm.nih.gov/pubmed/23277452
http://dx.doi.org/10.1084/jem.20111843
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author 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.
author_facet 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.
author_sort Zhang, Qibin
collection PubMed
description 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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spelling pubmed-35497052013-07-14 Serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes 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. J Exp Med Article 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. The Rockefeller University Press 2013-01-14 /pmc/articles/PMC3549705/ /pubmed/23277452 http://dx.doi.org/10.1084/jem.20111843 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
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.
Serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes
title Serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes
title_full Serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes
title_fullStr Serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes
title_full_unstemmed Serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes
title_short Serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes
title_sort serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549705/
https://www.ncbi.nlm.nih.gov/pubmed/23277452
http://dx.doi.org/10.1084/jem.20111843
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