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Peptide serum markers in islet autoantibody-positive children.
Diabetologia 60, 287-295 (2017)
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Autoantibody-positive; Autoimmunity; BABYDIAB/BABYDIET; LC-MS/MS; Progression time; Risk score; Selected reaction monitoring; Targeted proteomic; Type 1 diabetes