Melanie Shapiro laboratory

Genetics of Type 1 Diabetes Development and Immunotherapy Response

Human immune phenotyping reveals accelerated aging in type 1 diabetes


Journal article


Melanie R. Shapiro, Xiaoru Dong, Daniel J. Perry, James M. McNichols, P. Thirawatananond, A. Posgai, Leeana D. Peters, K. Motwani, Richard S. Musca, Andrew Muir, Patrick Concannon, Laura M. Jacobsen, Clayton E. Mathews, C. Wasserfall, Michael J. Haller, D. Schatz, Mark A. Atkinson, Maigan A. Brusko, Rhonda L. Bacher, T. Brusko
JCI Insight, 2023

Semantic Scholar DOI PubMedCentral PubMed
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APA   Click to copy
Shapiro, M. R., Dong, X., Perry, D. J., McNichols, J. M., Thirawatananond, P., Posgai, A., … Brusko, T. (2023). Human immune phenotyping reveals accelerated aging in type 1 diabetes. JCI Insight.


Chicago/Turabian   Click to copy
Shapiro, Melanie R., Xiaoru Dong, Daniel J. Perry, James M. McNichols, P. Thirawatananond, A. Posgai, Leeana D. Peters, et al. “Human Immune Phenotyping Reveals Accelerated Aging in Type 1 Diabetes.” JCI Insight (2023).


MLA   Click to copy
Shapiro, Melanie R., et al. “Human Immune Phenotyping Reveals Accelerated Aging in Type 1 Diabetes.” JCI Insight, 2023.


BibTeX   Click to copy

@article{melanie2023a,
  title = {Human immune phenotyping reveals accelerated aging in type 1 diabetes},
  year = {2023},
  journal = {JCI Insight},
  author = {Shapiro, Melanie R. and Dong, Xiaoru and Perry, Daniel J. and McNichols, James M. and Thirawatananond, P. and Posgai, A. and Peters, Leeana D. and Motwani, K. and Musca, Richard S. and Muir, Andrew and Concannon, Patrick and Jacobsen, Laura M. and Mathews, Clayton E. and Wasserfall, C. and Haller, Michael J. and Schatz, D. and Atkinson, Mark A. and Brusko, Maigan A. and Bacher, Rhonda L. and Brusko, T.}
}

Abstract

The proportions and phenotypes of immune cell subsets in peripheral blood undergo continual and dramatic remodeling throughout the human life span, which complicates efforts to identify disease-associated immune signatures in type 1 diabetes (T1D). We conducted cross-sectional flow cytometric immune profiling on peripheral blood from 826 individuals (stage 3 T1D, their first-degree relatives, those with ≥2 islet autoantibodies, and autoantibody-negative unaffected controls). We constructed an immune age predictive model in unaffected participants and observed accelerated immune aging in T1D. We used generalized additive models for location, shape, and scale to obtain age-corrected data for flow cytometry and complete blood count readouts, which can be visualized in our interactive portal (ImmScape); 46 parameters were significantly associated with age only, 25 with T1D only, and 23 with both age and T1D. Phenotypes associated with accelerated immunological aging in T1D included increased CXCR3+ and programmed cell death 1–positive (PD-1+) frequencies in naive and memory T cell subsets, despite reduced PD-1 expression levels on memory T cells. Phenotypes associated with T1D after age correction were predictive of T1D status. Our findings demonstrate advanced immune aging in T1D and highlight disease-associated phenotypes for biomarker monitoring and therapeutic interventions.


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