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Systematic Assessment of Immune Marker Variation in Type 1 Diabetes: A Prospective Longitudinal Study
Cate Speake1, Henry T Bahnson1, Johnna D Wesley2
1Benaroya Research Institute at Virginia Mason, Seattle, WA, United States.
Frontiers in Immunology
|October 2, 2019
Summary
Identifying reliable immune biomarkers for type 1 diabetes (T1D) is crucial. This study found that a limited number of immune analytes show consistent biological variability, suggesting their potential for stratifying patients and predicting outcomes.
Area of Science:
- Immunology
- Endocrinology
- Biomarker Discovery
Background:
- Type 1 diabetes (T1D) exhibits significant heterogeneity in disease progression, risk, and treatment response.
- Immune analytes are extensively studied for their potential as biomarkers in T1D.
- The clinical utility of these biomarkers hinges on their technical and biological variability and correlation with clinical outcomes.
Purpose of the Study:
- To assess the technical and biological variability of 91 immune analytes in adults with recent-onset T1D.
- To identify immune analytes with high between-subject and low within-subject variability for potential use in subject stratification.
- To pilot the use of intraclass correlation coefficient (ICC) for identifying analytes associated with biological outcomes like C-peptide levels.
Main Methods:
- A prospective study involving 91 immune analytes measured over 9-10 visits in 1 year for adults with T1D (<3 years from diagnosis).
- Evaluation included autoantibodies, T-cell, natural killer cell, and myeloid subsets, as well as autoreactive T-cell frequencies and function.
- Intraclass correlation coefficient (ICC) was calculated for each marker to assess variability; association with C-peptide was analyzed using partial least squares modeling.
Main Results:
- 35 out of 91 tested immune analytes demonstrated high between- and low within-subject variability, indicating potential for subject stratification.
- Extensive data on technical variability was provided for 64 analytes.
- CD8 effector memory T-cell (CD8 EM) frequency showed a high ICC and a positive correlation with C-peptide levels, validated in an independent dataset.
Conclusions:
- A limited number of technically reproducible immune analytes possess high ICC, making them suitable for biomarker studies.
- The study proposes using ICC to define variability and measure technical reproducibility for future biomarker identification in T1D.
- This approach is critical for selecting analytes in clinical trials to understand T1D heterogeneity and therapeutic responses.
