25(OH)D Levels in Infancy Is Associated With Celiac Disease Autoimmunity in At-Risk Children: A Case–Control Study

Abstract

Objectives: An observed variation in the risk of celiac disease, according to the season of birth, suggests that vitamin D may affect the development of the disease. The aim of this study was to investigate if vitamin D concentration is associated with the risk of celiac disease autoimmunity (CDA) in genetically at-risk children.Study Design: Children prospectively followed in the multinational The Environmental Determinants of Diabetes in the Young study, conducted at six centers in Europe and the US, were selected for a 1-to-3 nested case–control study. In total, 281 case–control sets were identified. CDA was defined as positivity for tissue transglutaminase autoantibodies (tTGA) on two or more consecutive visits. Vitamin D was measured as 25-hydroxyvitamin D [25(OH)D] concentrations in all plasma samples prior to, and including, the first tTGA positive visit. Conditional logistic regression was used to examine the association between 25(OH)D and risk of CDA.Results: No significant association was seen between 25(OH)D concentrations (per 5 nmol/L increase) and risk for CDA development during early infancy (odds ratio [OR] 0.99, 95% confidence interval [CI] 0.95–1.04) or childhood (OR 1.02, 95% CI 0.97–1.07). When categorizing 25(OH)D concentrations, there was an increased risk of CDA with 25(OH)D concentrations <30 nmol/L (OR 2.23, 95% CI 1.29, 3.84) and >75 nmol/L (OR 2.10, 95% CI 1.28–3.44) in early infancy, as compared with 50–75 nmol/L.Conclusion: This study indicates that 25(OH)D concentrations <30 nmol/L and >75 nmol/L during early infancy were associated with an increased risk of developing CDA in genetically at-risk children. The non-linear relationship raises the need for more studies on the possible role of 25(OH)D in the relation to celiac disease onset.

Corneal Langerhans cells in children with celiac disease

“…We also found a lower level of 25OHD in patients with CeD, consistent with a higher prevalence of vitamin D deficiency in children with newly diagnosed celiac disease 30 and a non-linear relationship between vitamin D deficiency and the development of CeD in at-risk children 31 . In a recent study of 200 Saudi adolescent girls with marked vitamin D deficiency a strong inverse correlation was observed between TtG and 25 OHD levels 32 .…”

Anti-tissue transglutaminase antibodies (TG2A) positivity and the risk of vitamin D deficiency among children - a cross-sectional study in the generation R cohort

“…Recently, Wessels et al reported that vitamin D status in relation to CeD might depend on more than a gluten free diet and vitamin D supplementation, since two-thirds of their patients remained vitamin D deficient after five-year follow up despite a prescription for vitamin D supplementation [ 42 ]. Interestingly, a study by Aronsson et al (2021) showed a U-shaped relation between vitamin D concentrations and risk of CeD, whereas our results showed no indication for non-linearity [ 43 ]. Specifically, they found that besides low vitamin D concentrations also vitamin D concentrations above 75 nmol/L, most likely due to frequent vitamin D supplementation, were associated with an increased risk of developing CeD, which might be explained by upregulation of Th2 cell cytokines associated with immune reaction to external stimuli by high doses of vitamin D [ 43 ].…”

“…Interestingly, a study by Aronsson et al (2021) showed a U-shaped relation between vitamin D concentrations and risk of CeD, whereas our results showed no indication for non-linearity [ 43 ]. Specifically, they found that besides low vitamin D concentrations also vitamin D concentrations above 75 nmol/L, most likely due to frequent vitamin D supplementation, were associated with an increased risk of developing CeD, which might be explained by upregulation of Th2 cell cytokines associated with immune reaction to external stimuli by high doses of vitamin D [ 43 ]. Our results do not support this hypothesis as we found no indication for non-linearity.…”

“…Our results do not support this hypothesis as we found no indication for non-linearity. To date, no clear consensus is reached regarding the optimal vitamin D concentration in childhood [ 43 ].…”

A meta-analysis suggests the association of reduced serum level of vitamin D and T-allele of Fok1 (rs2228570) polymorphism in the vitamin D receptor gene with celiac disease

“…During the early infant stage, 25(OH)D concentrations between <30 and >75 nmol/L were associated with an increased risk of developing CD in genetically predisposed children. The non-linear relationship raises the need for more studies on the possible role of 25(OH)D in the onset of CD ( 11 ). In vivo studies have shown a positive response to vitamin D supplementation in the celiac mice model ( 12 ).…”