Positive Deamidated Gliadin Peptide Antibodies and Negative Tissue Transglutaminase IgA Antibodies in a Pediatric Population: To Biopsy or Not To Biopsy

Abstract

Reports from our clinical laboratory database show that 75% of children <2 years old tested for celiac serology who were found positive for deamidated gliadin peptide (DGP) antibodies had negative results for tissue transglutaminase IgA. DGP levels were shown to decline and disappear without a gluten-free diet. This observation questions DGP's specificity for diagnosis of celiac disease.Celiac serology tests are the necessary tool for correctly referring individuals for duodenal biopsies when diagnosing celiac disease (4). Testing for tissue transglutaminase IgA (tTG) antibodies (Abs) is currently the test of choice used for this purpose (5, 17). Since there are reports indicating lack of tTG sensitivity in infants (3, 7), we decided that all serum samples from infants Ͻ2 years old referred to our clinical laboratory for celiac disease testing should be additionally tested for deamidated gliadin peptide (DGP) (IgG and IgA) Abs (6, 13). Gliadin Abs exhibit weak performance (4), and endomysial IgA (EMA) testing adds limited diagnostic value to the tissue transglutaminase (tTG) assay (12,19); therefore, these assays were not included in our laboratory practice. Total IgA was measured to identify IgA deficiency (5). In many cases, inconsistency between serology results, namely, DGP positive/tTG negative, was observed. We have retrospectively analyzed this observation by contacting the referring physicians and learning the clinical outcome for these infants.Over a period of 17 months (July 2007 to December 2008), we tested serum samples from 5,036 infants (Ͻ2 years old) for celiac disease-specific Abs using two commercial enzymelinked immunosorbent assay (ELISA) kits, one for DGP Abs (Quanta Lite DGP IgGϩIgA screen [Inova Diagnostics, San Diego, CA]: intraassay coefficient of variation [CV], 0.5 to 4.7%; interassay CV, 2.4 to 5.8%; standard deviation, 0.1 to 3.8) and one for tTG Abs (Celikey tTG-IgA; Phadia, Freiburg, Germany). We compiled reports from the laboratory's database, listing all infants with contradicting positive and negative results.The DGP results were positive in 202 infants; of these, only 35 (17%) were positive for tTG (Fig. 1). Positive results for both Ab entities are highly suggestive of celiac disease and indicate the desirability of performing duodenal biopsies. Since these cases were not of interest in our study, no further follow-up was conducted. IgA deficiency (IgA at Ͻ6 mg/dl, determined with a BNII nephelometer; Siemens) was determined in 15 (7.4%) infants. These infants were referred for biopsies in order to make a final diagnosis. In the remaining 152 (75%) infants, tTG was negative (Ͻ3 U/ml) (Fig. 1). We contacted the referring physicians in order to discover the clinical outcome in 80 of these cases with contradictory serology results. Twelve infants were referred for duodenal biopsies, mainly due to their physician's approach, claiming that when clinical features are present, one positive serology measurement is an adequate indication for performing biopsies. Celiac disease was diagn...

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

“…In the study by Olen and colleagues, [ 43 ] villous atrophy was found only in 8 of 149 children with DGP-positivity and tTG-negativity. These findings would suggest duodenal biopsy may be indicated in infants with sole anti-DGP positivity only if they have signs/symptoms consistent with CD and positivity for HLA DQ2/DQ8, as was the case in our patient [ 42 , 44 ].…”

“…The positivity of serum anti-DGPs only in very young children has a poor positive predictive value for CD and should be considered with caution: in a retrospective analysis, Parizade found that over 60% of children under 2 years of age with DGP-positive/tTG-negative pattern (HLA alleles not reported) became seronegative within 1 year, without following a gluten-free diet [ 42 ]. In that study, 6 out of 12 children with only anti-DGP positivity referred for biopsy, had a diagnosis of CD [ 42 ]. In the study by Olen and colleagues, [ 43 ] villous atrophy was found only in 8 of 149 children with DGP-positivity and tTG-negativity.…”

Celiac Disease Screening Assays for Children Younger than 3 Years of Age: The Performance of Three Serological Tests

“…Previous reports have indicated that positive serology can precede small intestinal mucosal atrophy indicating that children with positive EMA have a high probability of having CD, irrespective of negative biopsy [31][32][33]. On the other hand, some authors found that positive antibodies in young children decline over time without treatment with a gluten free diet, especially DGP serology [20,30,34]. In our cohort, a high percentage (77.8%) of patients with normal biopsy was positive for DGP only.…”

Assessing of Celiac Disease and Nonceliac Gluten Sensitivity

“…In this study sensitivities and specificities were 100% using 2 different IgG-DGP ELISA kits [ 81 ]. However, since it has been reported that some anti-DGP antibody positive children that are <2 years old became DGP antibody negative over time without maintaining a gluten-free diet, serological follow-up is recommended in this group of patients [ 101 ]. In general, due to the fact that performance of all CD-specific serology tests depends on the prevalence of the condition, the age of the subjects evaluated, and the amount of gluten ingested, these factors should be considered when interpreting CD-specific serology results.…”