Simultaneous detection of IgA and IgG antibodies against tissue transglutaminase: The preferred pre-biopsy test in childhood celiac disease

Abstract

OBJECTIVES: IgA antibodies against tissue transglutaminase (anti-TG2) is a reliable marker of celiac disease (CD). However, IgA-deficient patients are not identified and young children may lack IgA anti-TG2. Combined detection of IgA and IgG (IgA/IgG) against deamidated gliadin peptides (DGP) has shown a high diagnostic performance for untreated CD. Here we examined the utility of IgA/IgG anti-TG2, IgA/IgG anti-DGP and IgA/IgG against a mix of TG2 and DGP (anti-TG2/DGP) in finding CD among children. METHODS: Serum antibodies against TG2, DGP, and TG2/DGP were determined with ELISA in 242 children referred to a paediatric gastroenterologist. Fifty had untreated CD verified by an intestinal biopsy and 192/242 children had other diseases than CD. RESULTS: Forty-eight untreated CD children had increased IgA/IgG anti-TG2, 47/50 had increased IgA/IgG anti-DGP and 46/50 had increased IgA/IgG anti-TG2/DGP. One control subject had increased IgA/IgG anti-TG2 and IgA/IgG anti-TG2/DGP, whereas 7/192 control subjects had increased IgA/IgG anti-DGP. The IgA/IgG anti-TG2 assay had the best performance with a sensitivity of 96%, a specificity of 99.5% and the area under the ROC-curve was 0.996 (95% CI 0.992-1, p < 0.0001). CONCLUSIONS: Detection of one antibody is not sufficient when screening for untreated CD among children due to cases of IgA deficiency. The inclusion of DGP antigens in the IgA/IgG combination assays seems to affect the sensitivity and specificity negatively, whereas detection of IgA/IgG anti-TG2 has the potential of finding most untreated CD patients, including those with IgA deficiency.