A new study from the Celiac Disease Genomic, Environmental, Microbiome, and Metabolomics (CDGEMM) cohort is offering fresh insight into how celiac disease develops in early childhood and it may change how we think about the timing of diagnosis.
For the study, researchers followed more than 500 children from birth, all of whom had a parent or sibling with celiac disease, to better understand how and when immune markers appear before diagnosis. Specifically, they focused on tissue transglutaminase IgA (tTG-IgA), the primary antibody used in blood tests to screen for celiac disease.
What they found was striking. In children who eventually developed celiac disease, tTG-IgA levels were completely normal just six months before testing positive. In other words, antibody levels didn’t slowly creep upward, they spiked suddenly, signaling a rapid immune shift rather than a gradual buildup.
These findings challenge the assumption that very high antibody levels mean a delay in diagnosis. Instead, they suggest that for some children, the immune system can transition from tolerance to full activation against gluten in a matter of months.
“We were quite surprised to see some children go from having a completely normal tTG to having a tTG of nearly 5000 6 months later. This suggests that—at least in young children from families at risk of celiac disease—a very high tTG at diagnosis does not necessarily mean that the condition was present for a long time.” – Dr. Maureen Leonard, study author and Director of the Center for Celiac Disease Research and Treatment
For families and providers, this research offers important reassurance about repeat screening and ongoing follow up for children at risk for celiac disease. While this study focused on children under three years old, it adds to growing body of research about how celiac disease begins. Other studies from the CDGEMM team are exploring additional early biomarkers, such as antibodies to deamidated gliadin peptides (DGP) and markers of gut permeability like zonulin. Together, this research moves us closer to understanding the earliest signs of celiac disease and how we might one day predict, or even prevent, its onset.