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Published on: July 5, 2022
Serum proteomes distinguish children developing type 1 diabetes in a cohort with HLA-conferred susceptibility
Robert Moulder1, Santosh D Bhosale1, Timo Erkkilä2
1Turku Centre for Biotechnology, University of Turku, Turku, Finland.
Insights
Longitudinal serum proteomics identified key protein changes before type 1 diabetes autoantibodies appear. This discovery aids in early detection of diabetes susceptibility in children.
Area of Science:
- Immunology
- Proteomics
- Pediatrics
Background:
- Type 1 diabetes (T1D) is an autoimmune disease with a pre-clinical phase.
- Identifying biomarkers during the pre-diabetic period is crucial for early intervention.
Purpose of the Study:
- To identify longitudinal serum proteomic changes preceding autoantibody seroconversion in children with T1D susceptibility.
- To discover novel protein candidates indicative of impending T1D development.
Main Methods:
- Longitudinal serum samples from children (3 months to 12 years) with HLA-conferred T1D susceptibility were analyzed.
- Proteomics was performed using isobaric tags for relative and absolute quantification (iTRAQ) and label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) after serum protein depletion.
- Case-control analysis compared children who progressed to T1D with those who remained autoantibody-negative.
Main Results:
- Significant differences in the abundance of specific serum proteins were detected in progressors before autoantibody positivity.
- Classification of progressors was achieved with high accuracy using proteomic data.
- Temporal proteomic profiles were established for healthy children and those progressing to T1D.
Conclusions:
- Serum proteomic profiling can detect early signs of T1D development before clinical autoantibody markers.
- This study provides a valuable temporal proteomic reference and identifies potential new biomarkers for T1D prediction.
- Early detection through proteomic analysis holds promise for future T1D management strategies.
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.
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