Ulnes Maria, Lundbäck Veroniqa, Lindgren Susanne, Molin Mattias, Zetterström Rolf H, Ekwall Olov, Mårild Karl
Department of Pediatrics, Queen Silvia Children's Hospital, Gothenburg, Sweden.
Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
BMC Gastroenterol. 2025 Mar 11;25(1):159. doi: 10.1186/s12876-025-03743-z.
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.
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.
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.
Genetic and epigenetic markers for B cells and T cells in immune cell profiles at birth did not impact susceptibility to childhood-onset CD.
出生时免疫细胞谱在确定乳糜泻（CD）发病风险中的作用目前尚未明确。本研究旨在确定出生时T细胞和B细胞谱与儿童CD之间的关联。
这项区域性队列研究前瞻性分析了158例CD患儿（CD诊断时中位年龄7岁）以及两组匹配的对照者（每组n = 316）的干血斑样本。我们对T细胞受体切除环（TRECs）和κ链缺失重组切除环（KRECs）进行定量，以此作为出生时胸腺和骨髓输出的指标。此外，我们采用表观遗传细胞计数法来估计淋巴细胞亚群的百分比：CD3⁺、CD4⁺、CD8⁺ T细胞、CD4⁺ 记忆T细胞、调节性T细胞、B细胞和NK细胞。
未发现出生时检测的免疫细胞标志物与CD发病之间存在关联（所有p值> 0.26）。CD患者和对照者的TRECs拷贝数中位数分别为120（IQR = 92 - 168）和136（IQR = 91 - 183），KRECs的拷贝数中位数在CD患者中为69（IQR = 45 - 100），对照者为66（IQR = 44 - 93）。在所有组中，T细胞（CD患者为32.6% [IQR = 27.0 - 43.8%]，对照者为33.9% [IQR = 26.3 - 45.7%]）和B细胞（CD患者为25.4% [IQR = 20.3 - 30.6%]，对照者为24.7% [IQR = 19.9 - 30.8%]）的中位数百分比相似。CD患者与对照者之间淋巴细胞亚群估计值的比值接近1；所有p值均> 0.26。在按性别、HLA类型和诊断年龄定义的各亚组中，结果均一致。
出生时免疫细胞谱中B细胞和T细胞的遗传和表观遗传标志物不会影响儿童期CD的易感性。
