Peptide serum markers in islet autoantibody-positive children.
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.



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.



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.



Distinct peptide signatures indicate islet autoimmunity prior to the clinical manifestation of type 1 diabetes and enable refined staging of the presymptomatic disease period.
Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1, D-85764, München, Germany.
Christine
C
von Toerne
Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.|Department of Mathematics, Technische Universität München, Garching, Germany.
Michael
M
Laimighofer
Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1, D-85764, München, Germany.|Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.|Forschergruppe Diabetes e.V., Neuherberg, Germany.
Peter
P
Achenbach
Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1, D-85764, München, Germany.|Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Andreas
A
Beyerlein
German Center for Diabetes Research (DZD), Neuherberg, Germany.|Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
Tonia
T
de Las Heras Gala
Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
Jan
J
Krumsiek
Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.|Department of Mathematics, Technische Universität München, Garching, Germany.
Fabian J
FJ
Theis
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.|Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. anette-g.ziegler@helmholtz-muenchen.de.|Forschergruppe Diabetes e.V., Neuherberg, Germany. anette-g.ziegler@helmholtz-muenchen.de.
Anette G
AG
Ziegler
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.
Stefanie M
SM
Hauck
D000293:Adolescent; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism*; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000276:immunology / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology; D008297:Male; D010455:Peptides / Q000097:blood*; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry
D001323:Autoantibodies; D015415:Biomarkers; D007328:Insulin; D010455:Peptides
Autoantibody-positive; Autoimmunity; BABYDIAB/BABYDIET; LC-MS/MS; Progression time; Risk score; Selected reaction monitoring; Targeted proteomic; Type 1 diabetes