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Diabetes. 2015 Jun;64(6):2265-78. doi: 10.2337/db14-0983. Epub 2015 Jan 23.

Serum proteomes distinguish children developing type 1 diabetes in a cohort with HLA-conferred susceptibility.

Author information

1
Turku Centre for Biotechnology, University of Turku, Turku, Finland.
2
Department of Information and Computer Science, Aalto University School of Science, Espoo, Finland.
3
Department of Pediatrics, University of Turku, Turku, Finland Department of Pediatrics, Turku University Hospital, Turku, Finland.
4
School of Medicine, University of Tampere, Tampere, Finland Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland.
5
University of Oulu and Oulu University Hospital, Department of Pediatrics, Oulu, Finland.
6
Department of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland Immunogenetics Laboratory, University of Turku, Turku, Finland.
7
Department of Pediatrics, University of Turku, Turku, Finland Department of Pediatrics, Turku University Hospital, Turku, Finland Departments of Physiology and Pediatrics, University of Turku, Turku, Finland.
8
Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland Folkhälsan Research Institute, Helsinki, Finland.
9
Turku Centre for Biotechnology, University of Turku, Turku, Finland Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD.
10
Turku Centre for Biotechnology, University of Turku, Turku, Finland Department of Information and Computer Science, Aalto University School of Science, Espoo, Finland.
11
Turku Centre for Biotechnology, University of Turku, Turku, Finland riitta.lahesmaa@btk.fi.

Abstract

We determined longitudinal serum proteomics profiles from children with HLA-conferred diabetes susceptibility to identify changes that could be detected before seroconversion and positivity for disease-associated autoantibodies. Comparisons were made between children who seroconverted and progressed to type 1 diabetes (progressors) and those who remained autoantibody negative, matched by age, sex, sample periodicity, and risk group. The samples represented the prediabetic period and ranged from the age of 3 months to 12 years. After immunoaffinity depletion of the most abundant serum proteins, isobaric tags for relative and absolute quantification were used for sample labeling. Quantitative proteomic profiles were then measured for 13 case-control pairs by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Additionally, a label-free LC-MS/MS approach was used to analyze depleted sera from six case-control pairs. Importantly, differences in abundance of a set of proteins were consistently detected before the appearance of autoantibodies in the progressors. Based on top-scoring pairs analysis, classification of such progressors was observed with a high success rate. Overall, the data provide a reference of temporal changes in the serum proteome in healthy children and children progressing to type 1 diabetes, including new protein candidates, the levels of which change before clinical diagnosis.

PMID:
25616278
DOI:
10.2337/db14-0983
[Indexed for MEDLINE]
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