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

Carin Andrén Aronsson,Xiang Liu,Ulla Uusitalo,Beena Akolkar,William A Hagopian,Kalle Kurppa,Jorma Toppari,Daniel Agardh,Jin-Xiong She,Marian J Rewers,Martha D Butterworth,Jill M Norris,Sibylle Koletzko,Jeffrey P Krischer,Iris Erlund,Anette-G Ziegler,Suvi M Virtanen

doi:10.3389/fnut.2021.720041

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.

Highlights

Vitamin D is essential for bone growth and the effective functioning of innate immunity [1]
There was no association between 25(OH)D concentrations and risk for Celiac disease autoimmunity (CDA) development during early infancy or childhood, after adjusting for human leucocyte antigen (HLA), first degree relative (FDR) with celiac disease, season of birth, season of drawing blood, being on long-distance protocol (LDP), and islet autoimmunity (IA) status (Table 2)
Only a few subjects were exclusively breastfed and blood drawn was collected during the winter months (December to February). This nested case–control study found an association of low levels of 25(OH)D concentrations in early infancy with an increased risk of CDA in genetically at-risk children

Summary

Introduction

Vitamin D is essential for bone growth and the effective functioning of innate immunity [1]. Celiac disease is a chronic enteropathy with autoimmune features caused by an immune-mediated response to dietary gluten, leading to the destruction of intestinal mucosa resulting in malabsorption [9]. Children born during the spring and summer months are at the highest disease risk [16,17,18,19,20] This has led to the hypothesis that vitamin D deficiency in early life may predispose to celiac disease due to seasonal differences in UVB exposure and subsequent 25(OH)D concentrations or via dysregulation of the immune response leading to an abnormal intestinal mucosa with increasing permeability [21, 22]. Low 25(OH)D concentrations have been reported at the time of celiac disease diagnosis [23,24,25,26], this can be attributed to deranged dietary absorption from a damaged gut epithelium

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