Serologic Markers for Celiac Disease in Young Children

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Celiac disease (CD) is an autoimmune disease associated with small intestinal damage (villous atrophy and lymphocytic infiltration) in response to gluten ingestion. Although esophagogastroduodenoscopy (EGD) with duodenal biopsy is considered the “gold standard” test for confirming CD, the tissue transglutaminase IgA antibody titer (TTG IgA) is a highly sensitive and specific serum test for CD screening. National guidelines (such as from the Celiac Disease Foundation) do not recommend TTG IgA screening before 2 years of age because of concerns about testing sensitivity in that age group. The authors of this study tested this recommendation by reviewing medical records of children from 3 tertiary children’s hospitals in the United States. Two of the hospitals had retrospective records reviewed as far back as 20 years while the third hospital utilized a prospective database of children with villous atrophy diagnosed by EGD. All included patients were evaluated for diagnostic criteria for CD (including serologic markers of disease and duodenal biopsy findings), resolution of gastrointestinal symptoms on a gluten-free diet, and normalization of serologic markers for CD while on a gluten-free diet. Thus, patients with CD associated with positive serologic markers and positive duodenal biopsy findings were compared to a control group of children with duodenal biopsies consistent with CD but who had negative serologic findings and no gluten exposure or no response to a gluten-free diet.

A total of 150 children were included in the study for which 127 had CD and 23 belonged to the control group. The median age at time of duodenal biopsy was 18 months (range 3 – 24 months) with most children having a diagnosis of failure to thrive. Biopsies demonstrated intraepithelial lymphocytosis in 3% of children, partial villous atrophy in 45% of children, and total villous atrophy in 52% of children. Various CD serologic markers were ordered for these patients with TTG IgA being the most common test although other testing types included endomysium IgA, antigliadin IgA with / without IgG, and deamidated gliadin protein IgA with / without IgG. Of the 127 children with CD, 115 underwent TTG IgA testing for which 112 patients (97.5%) had elevated TTG IgA titers with the remaining 3 patients having positive TTG IgG titers. IgA deficiency was present in 5.5% of patients with CD although all such children had some type of positive IgG testing (such as TTG, anti-gliadin, or deamidated gliadin protein). Alternatively, 19 of the 23 children in the control group had TTG IgA testing performed, and all tests were negative. The remaining 4 children in the control group consisted of one patient with negative endomysium IgA testing and 3 children with no other serologic testing performed. When all patients with TTG IgA testing were compared, patients with CD were significantly older (19 months versus 15 months, P=0.001) and had a higher TTG IgA level (7.4 times the upper limit of normal versus 0.3 times the upper limit of normal, P<0.001).

This study, based on retrospective data, seems to indicate that TTG IgA testing may be an appropriate screen for CD in children younger than 2 years of age. The authors point out that IgG antibody testing may be indicated for those young patients with negative TTG IgA testing but with symptoms of CD.

Khan M, Silvester J, Sparks B, Hintze Z, Ediger T, Larson J, Hill I, Absah I. The utility of IgAbased serologic markers in diagnosing celiac disease in children 24 months of age or younger. Journal of Pediatrics 2020; 224: 158-161.

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