Coeliac disease in infants: antibodies to deamidated gliadin peptide come first!

Abstract

BackgroundThe onset of coeliac disease (CD) in the first year of life is uncommon and the diagnosis can be challenging due to the suboptimal sensitivity of tissue transglutaminase antibodies (tTG) at this age and the many other possible causes of malabsorption in infants. Antibodies to deamidated gliadin peptides (anti-DGPs), especially IgG, may appear earlier than IgA anti-tTG in very young children with CD.Case presentationWe report here on an 8-month-old child who was evaluated for failure to thrive, constipation and developmental delay. The symptoms started following gluten introduction in the diet. Laboratory tests showed high fecal elastase concentration, normal serum IgA levels with positive IgG and IgA anti-DGPs, whereas anti-tTG were not detected. The duodenal biopsy revealed a complete villous atrophy (Marsh-Oberhuber 3C). The culture of biopsy fragments in the presence of gliadin peptides did not stimulate the production of IgA anti-endomysial antibodies. Genetic testing proved the child was positive for HLA-DQ2 (DQA1*05; DQB1*02) and HLA-DQ8 (DQA1*03, DQB1*0302). Having initiated the gluten-free diet, the symptoms disappeared and the infant experienced rapid catch-up growth with normalization of psychomotor development.ConclusionsThis case report highlights the utility of anti-DGPs for screening infants with suspected CD. The pattern with positivity for IgG and IgA anti-DGPs only is rare in IgA-competent children with biopsy-proven CD. It could be explained in infancy as immaturity of the adaptive immune system.

Influence of Age and Type 1 Diabetes Mellitus on Serological Test for Celiac Disease in Children

“…The breakdown of 4 years of age was mainly based on the first quartile of age in the entire cohort. This was also within the range of age breakdown between 2 and 7 years in several previous studies [ 15 16 17 18 19 ]. 2) T1DM and non-T1DM groups: Patients were classified into the T1DM group if the diagnosis was reported in the patients' records by their endocrinologists based on standard criteria at the time of the initial serological tests.…”

“…Although TTG IgA is the obligatory test for correlation with histology and for screening at risk populations for CD in the presence of IgA sufficiency, there is a debate whether TTG IgA is a reliable test in younger children, given concerns about age-related changes in immunogenicity [ 15 16 ]. We showed that mean TTG IgA in the <4.0 years of age group was slightly but significantly lower than the ≥4.0 years of age group when analyzed in a normal non-CD cohort, suggesting there was an age-related difference in TTG IgA levels.…”

“…Although definitive diagnosis relies on intestinal biopsy, serological testing to measure CD-specific antibodies has been widely used to screen patients with suspected gluten sensitive enteropathy, as well as for monitoring dietary compliance [ 13 14 ]. The most commonly ordered antibody tissue transglutaminase (TTG) shows good specificity and sensitivity for histological findings in children [ 4 13 14 ], while other studies have demonstrated variable results in young children [ 15 16 ]. Recent studies suggest that deamidated gliadin peptide (DGP) antibodies had an increased diagnostic accuracy in young children [ 17 18 ], though others illustrated that it increased neither the sensitivity nor the specificity in predicting histology results compared with TTG antibodies [ 19 20 21 ].…”

Diagnosis of celiac disease in groups of genetic risk: modern view on the problem

“…Along with the regional genetic diversity of the human population and the nutritional characteristics observed in different countries, differences in the prevalence of celiac disease are due to the use of diagnostic tests with unequal specificity and sensitivity [17,18,19]. A retrospective study of blood samples from adult Americans taken in 1974, 1989, and 2001 showed that the incidence of serological markers of celiac disease in 1974 was 1:501, in 1989 -1:219, and in 2001 -1:105.…”

Protective Role of Breastfeeding in Children With Celiac Disease.

“…7 ,8 Several studies have suggested a protective role of breastfeeding and/or the timing and quantity of gluten introduction in the subsequent development of celiac disease. Especially, prolonged breastfeeding during the introduction of gluten-containing feeding has been associated with a reduced risk of developing celiac disease in infancy 9,10 . The mentioned results suggest the existence of a 'window of opportunity' between 4 and 6 months of age in which gluten can be introduced in small amounts 11 .…”