Diagnostic performance of IgG anti-deamidated gliadin peptide antibody assays is comparable to IgA anti-tTG in celiac disease
Introduction
Celiac disease is an autoimmune disorder characterized by a heightened immunological responsiveness to ingested gluten (from wheat, barley or rye) in genetically susceptible individuals [1], [2]. The exact mechanisms responsible for celiac disease are not fully understood. It is thought that selective deamidation of gliadin (which is rich in glutamine residues) by tTG to deamidated gliadin peptides (DGP) facilitates binding to MHC class II molecules, and thereby triggers a T cell-mediated immune response [3]. Furthermore, it has been shown that deamidation of gliadin increases the binding of anti-gliadin antibodies in serum of CD patients, but not of non-CD patients [4], [5].
The definitive diagnosis of celiac disease requires a small intestinal biopsy examination [6]. The detection of autoantibodies or antibodies against gliadin has often been used as first-line test to identify individuals who require a duodenal biopsy. Detection of IgA antibodies directed against endomysium or tissue transglutaminase (tTG), the target of anti-endomysial autoantibodies, is preferred over detection of IgG antibodies against endomysium, tTG or gliadin because of the higher sensitivity and specificity [7]. This was confirmed in two systematic reviews [8], [9]. A drawback of the detection of IgA antibodies for celiac disease, however, is that patients with a selective IgA deficiency will test false-negative.
In 2004, Schwertz et al. showed that the detection of antibodies against DGP could be a valuable tool for the diagnosis of celiac disease [10]. IgG anti-DGP antibodies are more sensitive and more specific for CD than IgG anti-gliadin antibodies[11] and their performance is at least as good as that of IgA anti-DGP antibodies [11], [12], [13]. The performance of IgG anti-DGP antibodies is also reported to be comparable to the performance of IgA anti-tTG [12], [13], although large studies examining this in consecutive adult and pediatric patients are lacking.
There are currently four manufacturers of commercially available IgG DGP assays: Euroimmun, Inova, Phadia and The Binding Site. Several authors have evaluated the performance of the Inova IgG anti-DGP assay [11], [12], [13], [14], [15], [16] and the Euroimmun assay in children [17], but there are no studies that have evaluated the assays from The Binding Site or Phadia or that have compared the performance of the different IgG anti-DGP assays. Previous studies also had limitations with respect to patient selection. In some studies, for example, only patients with more severe histological changes of the small bowel were included [11], [16]. Other studies included only a limited number of disease control patients or included selected control patients such as healthy blood donors [14], [15], [18]. These methodological flaws were highlighted in a recent systematic review on the performance of IgA anti-tTG and IgG anti-DGP [19]. Most studies were also restricted either to adults or children [12], [13], [15], [17], [20].
The aim of this study was to compare the performance of the four IgG anti-DGP assays to other serologic assays for celiac disease including 3 IgA anti-tTG assays in a large cohort of 86 consecutive CD patients and 741 consecutive disease control patients. The study population consisted of 599 adults and 228 children. All CD and control patients had a duodenal biopsy.
Section snippets
Study population
Patients attending the University Hospitals Leuven who had serologic tests for celiac disease and underwent an intestinal biopsy were identified retrospectively. The main reasons for performing these tests were diarrhea, weight loss, abdominal pain, anemia, anorexia, failure to thrive and small stature. Consecutive CD patients for whom serum was available were recruited over a 100-month period (between August 1st 2000 and November 31st 2008) and consecutive disease control patients over a
Linearity
We determined the linearity by diluting a sample that contained a high concentration of IgG anti-DGP antibodies with increasing amounts (from 0% to 100%) of a sample that was negative for IgG anti-DGP antibodies. The Euroimmun assay, which includes three standards, uses a 2-point linear fit for the negative results (standard 1 and 2) and a 2-point linear fit for the positive results (standard 2 and 3). The Phadia assay uses a Rodbard four parameter general curve fit using 5 standards. The assay
Discussion
In the present study, we evaluated four commercial IgG anti-DGP assays in a large cohort of 86 consecutive CD patients and 741 consecutive disease control patients and compared their diagnostic accuracy to other serologic assays for the diagnosis of celiac disease. The technical performance of the four IgG anti-DGP assays was acceptable. The diagnostic accuracy of the four IgG anti-DGP assays was comparable to the three IgA anti-tTG assays tested and better than the IgG anti-tTG, IgA
Acknowledgement
We thank Euroimmun, Inova, Phadia and The Binding Site for the generous donation of the assays.
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