Mass Screening for Celiac Disease: The Autoimmunity Screening for Kids Study

Abstract

Introduction: The Autoimmunity Screening for Kids (ASK) study is a large scale pediatric screening study in Colorado for celiac disease (CD) and type 1 diabetes. This is a report of the CD outcomes for the first 9,973 children screened through ASK.

Methods: ASK screens children aged 1-17 years for CD using 2 highly sensitive assays for tissue transglutaminase autoantibodies (TGA): a radiobinding (RBA) assay for IgA TGA and an electrochemiluminescence (ECL) assay that detects all TGA isotypes. Children who test positive on either assay are asked to return for confirmatory testing. Those with a confirmed RBA TGA level ≥ 0.1 (twice the upper limit of normal) are referred to the Colorado Center for Celiac Disease for further evaluation; all others are referred to primary care.

Results: Of the initial 9,973 children screened, 242 children were TGA+ by any assay. Of those initially positive, 185 children (76.4%) have completed a confirmation blood draw with 149 children (80.5%) confirming positive by RBA TGA. Confirmed RBA TGA+ was associated with a family history of CD (odds ratio [OR] = 1.83; 95% confidence interval 1.06-3.16), non-Hispanic white ethnicity (OR = 3.34; 2.32-4.79), and female sex (OR = 1.43; 1.03-1.98). Gastrointestinal symptoms of CD, assessed at the initial screening, were reported equally often among the RBA TGA+ vs TGA- children (32.1% vs 30.5%, P = 0.65).

Discussion: The initial results of this ongoing mass-screening program confirm a high prevalence of undiagnosed CD autoimmunity in a screened US population. Symptoms at initial screening were not associated with TGA status (see Visual abstract, Supplementary Digital Content 5, http://links.lww.com/AJG/B587).

Figure 1:. Screening and confirmation results for transglutaminase autoantibodies (TGA)

(Conf, confirmation; ECL, Electrochemiluminescence Assay; RBA, Radiobinding Assay; TGA, tissue transglutaminase)

Figure 2:. Association of confirmed radiobinding assay (RBA) tissue transglutaminase (TGA) + cases with demographic characteristics by logistic regression model

(AA, African American, NHW, Non-Hispanic White) ^A Model adjusted for age, sex, family history of celiac disease, and self-reported ethnicity and race. Odds ratio compare those who confirm positive by RBA to those who initially screened negative. ^B Reference groups included 2–5 yrs for age, male for sex, no family history of celiac disease, and Hispanic for race/ethnicity.

Figure 3:. Outcomes of participants referred for further evaluation

(EMA, endomysial autoantibody; F/U, follow up; GI, gastroenterology; GFD, gluten-free diet) European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) diagnosis requires high positive TGA and positive EMA per the 2020 guidelines. Biopsy proven celiac disease refers to Marsh 2 or greater. Potential celiac disese refers to positive TGA with Marsh 1 or lower. Empiric GFD refers to children placed on a GFD before diagnostic confirmation of celiac disease. Persistent autoimmunity refers to children with positive TGA and being followed on a gluten containing diet. TGA negative at follow up refers to children who had a negative serologic evaluation at their follow up assessment. Asymptomatic and no follow up refers to children reported to still have no symptoms and, therefore, have not returned for further assessment.