title: Serum proteomes distinguish children developing type 1 diabetes in a cohort with HLA-conferred susceptibility.
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.
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Turku, Finland.
authors.forename: Robert
authors.initials: R
authors.lastname: Moulder
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Turku, Finland.
authors.forename: Santosh D
authors.initials: SD
authors.lastname: Bhosale
authors.affiliation: Department of Information and Computer Science, Aalto University School of Science, Espoo, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Erkkilä
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Turku, Finland.
authors.forename: Essi
authors.initials: E
authors.lastname: Laajala
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Turku, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Salmi
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Turku, Finland.
authors.forename: Elizabeth V
authors.initials: EV
authors.lastname: Nguyen
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Turku, Finland.
authors.forename: Henna
authors.initials: H
authors.lastname: Kallionpää
authors.affiliation: Department of Pediatrics, University of Turku, Turku, Finland Department of Pediatrics, Turku University Hospital, Turku, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Mykkänen
authors.affiliation: Department of Pediatrics, University of Turku, Turku, Finland Department of Pediatrics, Turku University Hospital, Turku, Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Vähä-Mäkilä
authors.affiliation: School of Medicine, University of Tampere, Tampere, Finland Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Hyöty
authors.affiliation: University of Oulu and Oulu University Hospital, Department of Pediatrics, Oulu, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Veijola
authors.affiliation: Department of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland Immunogenetics Laboratory, University of Turku, Turku, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.affiliation: Department of Pediatrics, University of Turku, Turku, Finland Department of Pediatrics, Turku University Hospital, Turku, Finland.
authors.forename: Tuula
authors.initials: T
authors.lastname: Simell
authors.affiliation: 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.
authors.forename: Jorma
authors.initials: J
authors.lastname: Toppari
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland Folkhälsan Research Institute, Helsinki, Finland.
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Turku, Finland Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD.
authors.forename: David R
authors.initials: DR
authors.lastname: Goodlett
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Turku, Finland Department of Information and Computer Science, Aalto University School of Science, Espoo, Finland.
authors.forename: Harri
authors.initials: H
authors.lastname: Lähdesmäki
authors.affiliation: Department of Pediatrics, University of Turku, Turku, Finland Department of Pediatrics, Turku University Hospital, Turku, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Simell
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Turku, Finland riitta.lahesmaa@btk.fi.
authors.forename: Riitta
authors.initials: R
authors.lastname: Lahesmaa
mesh_terms: D001798:Blood Proteins / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000378:metabolism*; D004198:Disease Susceptibility; D005260:Female; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D011236:Prediabetic State / Q000097:blood / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D001798:Blood Proteins; D006680:HLA Antigens