Exploring the Role of Newborn Immune Markers in Celiac Disease Development

Celiac.com 04/24/2025 - Celiac disease is an autoimmune disorder triggered by gluten consumption, leading to damage in the small intestine. While genetic factors, particularly certain HLA types, are known to play a significant role in predisposing individuals to celiac disease, the role of immune cell profiles at birth remains unclear. This study aimed to investigate whether specific immune cell markers at birth could influence the risk of developing celiac disease in childhood. By analyzing dried blood spots collected at birth, researchers explored the potential connections between immune cell profiles and the later onset of celiac disease.

Study Design and Participants

The study involved a regional cohort of 158 children diagnosed with celiac disease, with a median age of seven years at diagnosis. Each child with celiac disease was matched with two healthy comparators, resulting in a total of 316 comparators. The researchers analyzed dried blood spots collected at birth to measure specific immune markers, including T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs), which reflect the output of T cells and B cells from the thymus and bone marrow, respectively. Additionally, epigenetic cell counting was used to estimate the percentages of various lymphocyte subsets, such as T cells, B cells, and natural killer (NK) cells.

Key Findings

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No Significant Associations Found:
The study found no significant differences in immune cell markers at birth between children who later developed celiac disease and those who did not. TREC and KREC levels, as well as the percentages of T cells, B cells, and NK cells, were similar across both groups. This suggests that immune cell profiles at birth do not play a significant role in determining the risk of celiac disease.

Consistency Across Subgroups:
The results remained consistent when analyzed by sex, HLA type, and age at diagnosis. This further supports the conclusion that immune cell profiles at birth are not predictive of celiac disease development.

Comparison with Other Autoimmune Diseases:
Unlike some other autoimmune conditions, such as juvenile idiopathic arthritis (JIA) and immune thrombocytopenia (ITP), which have been linked to low TREC levels, celiac disease showed no such association. This highlights the unique nature of celiac disease in terms of its immunological triggers.

Discussion

The study’s findings challenge the hypothesis that immune cell profiles at birth significantly influence the risk of developing celiac disease. While other autoimmune conditions have shown associations with low TREC or KREC levels, celiac disease appears to be an exception. This suggests that the mechanisms driving celiac disease may differ from those of other autoimmune disorders.

Environmental factors, such as infections, diet, and gut microbiome composition, have been proposed as potential contributors to celiac disease development. However, this study did not find evidence that immune cell profiles at birth interact with these factors to increase disease risk. Instead, the findings point to the importance of genetic predisposition, particularly HLA types, as the primary determinant of celiac disease susceptibility.

The study also highlights the potential role of early-life immune system development in shaping disease risk. While immune cell profiles at birth may not be predictive, changes in the immune system during the first few months of life could still play a role. For example, previous research has identified specific lipid and cytokine patterns in infants who later develop celiac disease, suggesting that early immune system maturation may be a critical period for disease development.

Strengths and Limitations

The study’s strengths include its use of a novel epigenetic cell counting technique to analyze dried blood spots, which allowed for the examination of prospectively collected samples. The large, well-defined cohort of children with celiac disease and the matched comparator design also add robustness to the findings.

However, the study has some limitations. For ethical reasons, the researchers were unable to collect HLA type and medical history data for the comparators, which could have provided additional insights. Additionally, the median age at diagnosis was seven years, so the findings may not apply to children with very early-onset celiac disease. Finally, while the study focused on the quantity and proportion of immune cells, it did not explore potential functional differences that could influence disease risk.

Conclusion and Implications for Celiac Disease Patients

This study provides valuable insights into the early-life factors that may or may not contribute to the development of celiac disease. By demonstrating that immune cell profiles at birth do not significantly influence disease risk, the findings underscore the importance of genetic predisposition and environmental factors in celiac disease development.

For individuals with celiac disease, this research reinforces the importance of early diagnosis and management, particularly for those with a family history of the condition. While immune cell profiles at birth may not predict disease risk, understanding the genetic and environmental triggers of celiac disease can help guide preventive measures and personalized treatment strategies. Future research should continue to explore the role of early-life immune system development and environmental exposures in shaping disease risk, with the ultimate goal of improving outcomes for individuals with celiac disease.

Read more at: bmcgastroenterol.biomedcentral.com