Serologically atypical coeliac disease patients

Are coeliac disease (CD) patients underdiagnosed if they test negative for IgA-antibodies against transglutaminase 2 (TG2-IgA) despite IgA competence? Could testing of IgG-antibodies against deamidated gliadin peptides (DGP-IgG) help? Do such atypical patients exist?

In general, the widespread use of the TG2-IgA assay for screening means that IgA-competent CD patients negative for TG2-IgA antibodies are at risk of underdiagnosis and findings on TG2-IgA negative but IgG-DGP positive CD patients are difficult to obtain.

In a paper published recently in this journal [1], Bufler et al. provide valuable insights into the performance of serological tests from different manufacturers. Unfortunately, the authors claim that “combined testing for TG2-IgA and DGP-IgG does not increase the detection rate of CD in IgA competent children compared to TG2-IgA only”. In their study, however, they considered 59 CD patients, 53 of whom had already tested positive for TG2-IgA and the remaining 6 for EMA. They thus essentially excluded atypical patients from the outset.

Although the authors themselves admit that results on diagnostic characteristics may be biased by initial screening with a TG2-IgA assay, they drew a conclusion that cannot be drawn from the evidence they provide.

There is indeed evidence for the existence of atypical CD patients. There are occasional reports on IgA-competent CD patients negative for TG2-IgA in adults [2-4]. In children findings are rarer, but in two recent papers, 2 and 3 cases were reported [5],[6]. Until now, the low number of cases does not permit judgement regarding the potential usefulness of DGP-IgG in increasing the sensitivity of serological diagnosis of CD. Further studies are necessary to answer this question.

Conflict of interest

Thomas Mothes shares in a patent of DGP antibody assays. All other authors have declared that no competing interests exist.

• Literature

• 1 Bufler P, Heilig G, Ossiander G et al. Diagnostic performance of three serologic tests in childhood celiac disease. Z Gastroenterol 2015; 53: 108-114
• 2 Dahle C, Hagman A, Ignatova S et al. Antibodies against deamidated gliadin peptides identify adult coeliac disease patients negative for antibodies against endomysium and tissue transglutaminase. Aliment Pharmacol Ther 2010; 32: 254-260
• 3 Sugai E, Hwang J, Vazquez H et al. New Serology Assays Can Detect Gluten Sensitivity among Enteropathy patients seronegative for anti–tissue transglutaminase. Clin Chem 2010; 56: 661-665
• 4 Rashtak S, Ettore MW, Homburger HA et al. Comparative usefulness of deamidated gliadin antibodies in the diagnosis of celiac disease. Clin Gastroenterol Hepatol 2008; 6: 426-432
• 5 Wolf J, Hasenclever D, Petroff D et al. Antibodies in the diagnosis of coeliac disease: A biopsy-controlled, international, multicentre study of 376 children with coeliac disease and 695 controls. PLoS ONE 2014; 9: e97853
• 6 Oyaert M, Vermeersch P, de Hertogh G et al. Combining antibody tests and taking into account antibody levels improves serologic diagnosis of celiac disease. Clin Chem Lab Med 2015; DOI: 10.1515/cclm-2013-1099.