Background
The Western diet is associated with low‑grade systemic inflammation and altered immune regulation. However, evidence that a gluten-containing diet (GCD) increases systemic inflammation is limited.
Aim
To determine whether a GCD promotes early inflammation responses and the development of celiac disease autoimmunity (CDA) in genetically at-risk infants.
Methods
Fifty-two HLA-DQ2/DQ2 children were included from the Prevention of Celiac in Skåne (PreCiSe; NCT03562221); 17 (32.7%) children were randomized to an intervention with gluten-free diet (GFD) for 3 years and 35 (67.3%) children to a GCD. For this study, children were screened every 3 months for tissue transglutaminase autoantibodies (tTGA) from age 4 months to a mean age 4.9 (SD 1.5) years. Children with persistent tTGA was defined as having CDA. Nine plasma cytokines (IFN-y, IL-10, IL-12p70, IL-17A, IL-1ß, IL-2, IL-4, TNF-α, IL-6) were analyzed using MSD S-PLEX Proinflammatory Panel at age 4 and 18 months. Daily gluten intake was calculated at 18 months of age. Change in biomarker values were analyzed using linear regression adjusting for baseline value and gluten intake.
Results
Seventeen children in the GCD group developed CDA at median of 27.8 months (IQR 21.4-37.8) compared with none in the GFD group (p<0.001). At 18 months, gluten intake was higher in children who developed CDA compared with those who remained CDA-negative (4.2 vs 2.8 grams, p=0.023). In CDA children, cytokine levels from 4 to 18 months decreased for IL-1β (p=0.004), IL-4 (p=0.002), and TNF-α (p<0.001), while IFN-y increased (p=0.023). No changes were observed in the GFD group or among CDA-negative children in the GCD group.
Conclusion
Progression to CDA was associated with higher gluten intake and distinct longitudinal changes in immune-regulatory cytokines, suggestive of a shift toward a Th1-skewed immune response. These alterations were not observed in children following a GFD or children on GCD who remained CDA-negative.