Peptide serum markers in islet autoantibody-positive children

doi:10.1007/s00125-016-4150-x

. 2017 Feb;60(2):287-295.

doi: 10.1007/s00125-016-4150-x. Epub 2016 Nov 4.

Peptide serum markers in islet autoantibody-positive children

Christine von Toerne¹, Michael Laimighofer^{2

3}, Peter Achenbach^{4

5

6}, Andreas Beyerlein^{4

5}, Tonia de Las Heras Gala^{7

8}, Jan Krumsiek^{2

7}, Fabian J Theis^{2

3}, Anette G Ziegler^{9

10

11}, Stefanie M Hauck¹²

Affiliations

¹ Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1, D-85764, München, Germany.
² Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
³ Department of Mathematics, Technische Universität München, Garching, Germany.
⁴ Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1, D-85764, München, Germany.
⁵ Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
⁶ Forschergruppe Diabetes e.V., Neuherberg, Germany.
⁷ German Center for Diabetes Research (DZD), Neuherberg, Germany.
⁸ Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
⁹ Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1, D-85764, München, Germany. anette-g.ziegler@helmholtz-muenchen.de.
¹⁰ Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. anette-g.ziegler@helmholtz-muenchen.de.
¹¹ Forschergruppe Diabetes e.V., Neuherberg, Germany. anette-g.ziegler@helmholtz-muenchen.de.
¹² Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1, D-85764, München, Germany. hauck@helmholtz-muenchen.de.

PMID: 27815605
DOI: 10.1007/s00125-016-4150-x

Peptide serum markers in islet autoantibody-positive children

Christine von Toerne et al. Diabetologia. 2017 Feb.

. 2017 Feb;60(2):287-295.

doi: 10.1007/s00125-016-4150-x. Epub 2016 Nov 4.

Authors

Affiliations

¹ Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1, D-85764, München, Germany.
² Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
³ Department of Mathematics, Technische Universität München, Garching, Germany.
⁴ Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1, D-85764, München, Germany.
⁵ Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
⁶ Forschergruppe Diabetes e.V., Neuherberg, Germany.
⁷ German Center for Diabetes Research (DZD), Neuherberg, Germany.
⁸ Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
⁹ Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1, D-85764, München, Germany. anette-g.ziegler@helmholtz-muenchen.de.
¹⁰ Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. anette-g.ziegler@helmholtz-muenchen.de.
¹¹ Forschergruppe Diabetes e.V., Neuherberg, Germany. anette-g.ziegler@helmholtz-muenchen.de.
¹² Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1, D-85764, München, Germany. hauck@helmholtz-muenchen.de.

PMID: 27815605
DOI: 10.1007/s00125-016-4150-x

Abstract

Aims/hypothesis: We sought to identify minimal sets of serum peptide signatures as markers for islet autoimmunity and predictors of progression rates to clinical type 1 diabetes in a case-control study.

Methods: A double cross-validation approach was applied to first prioritise peptides from a shotgun proteomic approach in 45 islet autoantibody-positive and -negative children from the BABYDIAB/BABYDIET birth cohorts. Targeted proteomics for 82 discriminating peptides were then applied to samples from another 140 children from these cohorts.

Results: A total of 41 peptides (26 proteins) enriched for the functional category lipid metabolism were significantly different between islet autoantibody-positive and autoantibody-negative children. Two peptides (from apolipoprotein M and apolipoprotein C-IV) were sufficient to discriminate autoantibody-positive from autoantibody-negative children. Hepatocyte growth factor activator, complement factor H, ceruloplasmin and age predicted progression time to type 1 diabetes with a significant improvement compared with age alone.

Conclusion/interpretation: Distinct peptide signatures indicate islet autoimmunity prior to the clinical manifestation of type 1 diabetes and enable refined staging of the presymptomatic disease period.

Keywords: Autoantibody-positive; Autoimmunity; BABYDIAB/BABYDIET; LC-MS/MS; Progression time; Risk score; Selected reaction monitoring; Targeted proteomic; Type 1 diabetes.

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References

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1. Clin Chem. 2010 Feb;56(2):291-305 - PubMed
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[1] J Diabetes Complications. 2004 Jul-Aug;18(4):193-7 - PubMed

[2] J Diabetes Complications. 2004 Jul-Aug;18(4):193-7 - PubMed

[3] Clin Chem. 2010 Feb;56(2):291-305 - PubMed

[4] Clin Chem. 2010 Feb;56(2):291-305 - PubMed

[5] Diabetes. 2010 Jan;59(1):200-9 - PubMed

[6] Diabetes. 2010 Jan;59(1):200-9 - PubMed

[7] Arterioscler Thromb Vasc Biol. 2016 Mar;36(3):429-38 - PubMed

[8] Arterioscler Thromb Vasc Biol. 2016 Mar;36(3):429-38 - PubMed

[9] Diabetologia. 2012 Jul;55(7):1926-36 - PubMed

[10] Diabetologia. 2012 Jul;55(7):1926-36 - PubMed

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Peptide serum markers in islet autoantibody-positive children

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Peptide serum markers in islet autoantibody-positive children

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