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Electrochemiluminescence Assays for Human Islet Autoantibodies
Published on: March 23, 2018
Peptide serum markers in islet autoantibody-positive children
Christine von Toerne1, Michael Laimighofer2,3, Peter Achenbach4,5,6
1Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1, D-85764, München, Germany.
Insights
Minimal peptide signatures in serum can identify islet autoimmunity and predict type 1 diabetes progression. Two specific peptides effectively distinguish between autoantibody-positive and negative children, aiding early disease detection.
Area of Science:
- Proteomics
- Immunology
- Metabolomics
Background:
- Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic beta cells.
- Early identification of islet autoimmunity is crucial for understanding disease progression and developing interventions.
- Biomarkers are needed to detect T1D before clinical symptoms manifest.
Purpose of the Study:
- To identify minimal serum peptide signatures for detecting islet autoimmunity.
- To find predictors of progression to clinical T1D.
- To refine staging of presymptomatic T1D.
Main Methods:
- Shotgun and targeted proteomics were used on samples from children in the BABYDIAB/BABYDIET birth cohorts.
- A double cross-validation approach was employed to prioritize peptides.
- Analysis included 45 children for initial peptide prioritization and 140 for targeted validation.
Main Results:
- Forty-one peptides, enriched in lipid metabolism, differed significantly between autoantibody-positive and negative children.
- Two peptides (apolipoprotein M and apolipoprotein C-IV) were sufficient to discriminate between these groups.
- Hepatocyte growth factor activator, complement factor H, ceruloplasmin, and age predicted T1D progression more accurately than age alone.
Conclusions:
- Distinct serum peptide signatures indicate islet autoimmunity before clinical T1D onset.
- These signatures enable refined staging of the presymptomatic disease period.
- Peptide-based biomarkers offer potential for early T1D detection and monitoring.
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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