IgG antibodies against deamidated gliadin peptides for diagnosis of celiac disease in patients with IgA deficiency.

BACKGROUND: Assays for IgG antibodies against deamidated gliadin (IgG-anti-dGli) are comparable in performance with tests detecting IgA antibodies against tissue transglutaminase (IgA-anti-tTG) in diagnosing celiac disease (CD). IgA-anti-tTG are absent in IgA deficiency, a condition often associated with CD. In IgA deficiency, IgG-anti-tTG, which have a lower overall diagnostic accuracy, are routinely measured. We examined whether IgG-anti-dGli would be useful for diagnosing CD in patients with IgA deficiency. METHODS: We studied 34 IgA-deficient CD patients, 185 IgA-competent newly diagnosed children with CD, 316 children without CD, 400 adult blood donors, and 6 control IgA-deficient individuals without CD. Anti-dGli and anti-tTG were measured by ELISA, and endomysium antibodies (EmA) were measured by immunofluorescence on monkey esophagus (IgA as well as IgG class for all antibodies). We calculated diagnostic sensitivity (percentage of patients above cutoff with 95% CIs) according to age-specific cutoffs for 95% diagnostic specificity and according to cutoffs proposed by the manufacturer of the assays. RESULTS: No IgA-deficient CD patients were positive for any IgA-based antibody assay. Diagnostic sensitivity of IgG-anti-tTG was 91.2% (95% CI 76.3%-97.7%) according to age-specific cutoffs and 82.4% (66.1%-92.0%) according to manufacturer cutoffs. The diagnostic sensitivity of IgG-EmA was 75.8% (58.8%-87.4%) and the sensitivity of IgG-anti-dGli was 88.2% (72.8%-95.9%) according to both cutoffs. CONCLUSIONS: IgG-anti-dGli and IgG-anti-tTG have comparable diagnostic sensitivities for IgA-deficient celiac patients. IgG-anti-dGli may be useful for diagnosing CD in IgA-deficient patients.

New developments in serodiagnosis of childhood celiac disease: assay of antibodies against deamidated gliadin.

Antibodies to deamidated gliadin present a new tool in the diagnosis of celiac disease (CD). In children, the ELISA for the determination of IgG antibodies to (deamidated) gliadin-analogous fusion peptides (GAF3X) has a superior performance compared to the ELISA for the determination of antibodies against native gliadin and is comparable to assays for IgA antibodies against tissue transglutaminase (IgA-anti-tTG). The combined investigation of IgG antibodies to GAF3X (IgG-anti-GAF3X) and IgA-anti-tTG significantly increases the fraction of children definitely identified as either CD or non-CD patients. The new IgG-anti-GAF3X ELISA was also able to detect CD in three cases of IgA deficiency and in two cases of latent CD and was also useful in the diagnosis of children younger than 2 years of age.

Antibodies against deamidated gliadin as new and accurate biomarkers of childhood coeliac disease.

OBJECTIVES: Assays of tissue transglutaminase antibodies (anti-tTG) represent the cornerstone of serological coeliac disease (CD) diagnostics. Assays of antibodies against native gliadin (anti-nGli) lost importance due to low validity. We investigated the performance of new assays for antibodies against deamidated gliadin (anti-dGli) in childhood CD. METHODS: We retrospectively compared children (142 with active CD and 160 without CD, diagnosis confirmed or excluded by intestinal biopsy) concerning (immunoglobulin [Ig] G and IgA) anti-nGli, anti-tTG, and 2 different anti-dGli assays. RESULTS: IgG-anti-dGli1, IgG-anti-dGli2, and IgA-anti-tTG performed similarly. Area under the receiver-operating characteristic curve (AUC) was 98.6%, 98.9%, and 97.9%; accuracy was 94.7%, 95.7%, and 96.7%. Anti-dGli1 and anti-dGli2 (IgG and IgA) and IgA-anti-tTG performed significantly better than IgA-anti-nGli and IgG-anti-nGli. Both IgG-anti-dGli showed higher AUC and accuracy than IgA-anti-dGli and IgG-anti-tTG. Combined evaluation of IgA-anti-tTG with one of the IgG-anti-dGli tests reduced the rate of falsely classified patients. At enhanced cutoff (specificity >99%), sensitivity was above 67% for both IgG-anti-dGli and IgA-anti-tTG. If IgA-anti-tTG assay was combined with one of the IgG-anti-dGli tests, then the fraction of patients identified with more than 99% specificity as coeliacs increased significantly above 84.5%. Combined evaluation of the 2 IgG-anti-dGli tests did not improve the performance. CONCLUSIONS: The new IgA and IgG-anti-dGli tests outperform conventional anti-nGli assays. The validity of IgG-anti-dGli cannot be distinguished from IgA-anti-tTG. It should be studied prospectively whether antibody assays could replace biopsy in diagnosis of CD in a substantial segment of children.