The identification of celiac disease in asymptomatic children: the Generation R Study

Abstract

Background: The objective of our study was to assess whether TG2A levels in the healthy childhood population can be predictive of subclinical CD.

Methods: A total of 4442 children (median age, 6.0 years) participating in a population-based prospective cohort study were screened on serum TG2A. Those with positive TG2A (≥7 U/ml; n = 60, 1.4%) were invited for clinical evaluation (median age, 9.0 years). Medical history, physical examination, serum TG2A, and IgA-endomysium (EMA) were assessed, as well as HLA DQ 2.2/2.5/8 typing. Patients with positive serologies and genetic risk types underwent duodenal biopsies. TG2A levels at the time of biopsy were compared with the degree of enteropathy.

Results: Fifty-one TG2A-positive children were included in the follow-up: 31 (60.8%) children had CD, ten (19.6%) did not have CD, and ten (19.6%) were considered potential CD cases because of inconclusive serologies. Duodenal biopsies were performed in 26/31 children. CD with Marsh 3a/b enteropathy was observed in 75% (15/20) of children having TG2A levels ≥10ULN at 6 years of age, as well as in 75% (6/8) of children having a positive TG2A <10 ULN (OR 1.00; 95% CI 0.15-6.64). CD cases had a lower BMI SDS (mean -0.49, SD 0.92) than children without CD (mean 0.47, SD 1.37; p = 0.02). No differences were observed in gastrointestinal symptoms.

Conclusions: Serum TG2A screening at 6 years of age in the healthy childhood population has a positive predictive value of 61% to detect subclinical CD. We did not find a positive correlation between serum TG2A levels and the degree of enteropathy.

Keywords: Celiac disease; Child; Cohort study; Screening; Tissue transglutaminase type 2 antibodies.

Conflict of interest statement

Conflict of interest

The authors have no conflicts of interest to disclose.

Funding

This phase of the Generation R Study was supported by the Erasmus MC, Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), and by NutsOhra. The sponsors had no role in the design of the study; the data collection and analyses; the interpretation of data; the preparation and review of the manuscript; and the decision to submit the manuscript.

Financial disclosure

The authors have no financial relationships relevant to this article to disclose.

Figures

Fig. 1

Outcome of screening for anti-tissue transglutaminase antibodies (TG2A) in a population-based prospective cohort study. Sixty children had a positive TG2A test result at 6 years of age; 31/51 (60.8%) children were considered to have CD, 10/51 (19.6%) children needed follow-up, and 10/51 (19.6%) children did not have CD

Fig. 2

Serum TG2A concentrations at 6 and 9 years of age according to celiac disease diagnosis. Thin dotted line indicates clinical cutoff for IgA-TG2A positivity (≥7 U/ml). a TG2A concentrations between 6–9 years in CD group, bold line reflects n=14 CD cases who had strong positive IgA-TG2A concentrations (>125 U/ml at 6 years of age, and >128 U/ml at 9 years of age). b TG2A concentrations between 6–9 years in potential CD group. c TG2A concentrations between 6–9 years in children who lacked criteria for CD diagnosis. Four children were excluded because of negative genetic risk type. In addition, three children who received a CD diagnosis between 6 and 9 years of age were excluded from this figure

Fig. 3

Association between serum IgA-TG2A concentrations and the degree of enteropathy in children with undiagnosed celiac disease. a TG2A concentrations at 6 years of age according to Marsh–Oberhuber classification. b TG2A concentrations at 9 years of age to Marsh–Oberhuber classification. The three children who received a CD diagnosis between 6 and 9 years of age were excluded from this figure