Background: The role of immune cell profiles at birth in determining the risk of celiac disease (CD) development is currently unestablished. This study aimed to determine the associations between T- and B-cell profiles at birth and pediatric CD.
Methods: This regional cohort study analyzed prospectively collected dried blood spots from 158 children with CD (median 7 years old at CD diagnosis) and two matched comparators each (n = 316). We quantified T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) as measures of thymic and bone marrow output at birth. Moreover, we used epigenetic cell counting to estimate the percentages of lymphocyte subsets: CD3+, CD4+, CD8 + T cells, CD4 + memory T, regulatory T, B, and NK cells.
Results: No associations were found between measured immune cell markers at birth and CD development (all p values > 0.26). The median number of copies was 120 for TRECs (IQR = 92-168) and 136 (IQR = 91-183) for CD patients and comparators, respectively, and for KRECs, it was 69 (IQR = 45-100) for CD patients and 66 for comparators (IQR = 44-93). Across the groups, there were similar median percentages of T cells (CD, 32.6% [IQR = 27.0-43.8%] vs. comparators, 33.9% [IQR = 26.3-45.7%]) and B cells (CD, 25.4% [IQR = 20.3-30.6%] vs. comparators, 24.7% [IQR = 19.9-30.8%]). The ratio of the lymphocyte subset estimates between CD patients and comparators approximated one; all p values were > 0.26. The results were consistent across strata defined by sex, HLA type, and age at diagnosis.
Conclusion: Genetic and epigenetic markers for B cells and T cells in immune cell profiles at birth did not impact susceptibility to childhood-onset CD.
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http://dx.doi.org/10.1186/s12876-025-03743-z | DOI Listing |
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School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, P. R. China.
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Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, United States.
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Center for Translational Immunology, Benaroya Research Institute, Seattle, WA, United States.
The CD2-depleting drug alefacept (LFA3-Ig) preserved beta cell function in new-onset type 1 diabetes (T1D) patients. The most promising biomarkers of response were late expansion of exhausted CD8 T cells and rare baseline inflammatory islet-reactive CD4 T cells, neither of which can be used to measure responses to drug in the weeks after treatment. Thus, we investigated whether early changes in T cell immunophenotypes could serve as biomarkers of drug activity.
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