Comparison of the Reliability of 17 Celiac Disease Associated Bio-Markers to Reflect Intestinal Damage

Abstract

In view of the increasing importance of serological biomarkers for screening and diagnosing celiac disease (CD) and the lack of back-to-back comparison of their differential performance to their reliability to reflect the intestinal damage in children with CD, their performances were evaluated. 95 pediatric CD patients (mean age 8.3), 45 nonspecific abdominal pain children (AP) (mean age 7.3), 99 normal children (NC) (mean age 8.5) were tested with following ELISAs (detecting IgA, IgG or both, IgA and IgG (check)): AESKULISA® Gliadin (AGA), AESKULISA® DGP (DGP), AESKULISA® tTg “New Generation” (Neo-epitope tTg complexed to gliadin=tTg-neo), tTg (for in house research purpose only), AESKULISA® mTg neo-epitope and mTg (RUO). Anti-endomysial antibodies (EMA) were checked via immunofluorescence test. Results were compared to the degree of intestinal injury, using the revised Marsh criteria. Scatter diagrams and regression analysis comparing the 17 antibodies’ activities to the degree of the intestinal damage were performed. Most of the assays were able to discriminate patients with low and high degree of intestinal damage. Comparing the different correlations of CD associated IgA and IgG antibodies’ isotypes, the tTg-neo IgA (r2=0.6165, p<0.0001) and tTg-neo check (r2=0.6492, p<0.0001) stood out, significantly, as the best indicators for intestinal damage in CD. EMA-IgA, tTg, DGP checks and mTg-neo IgG correlated closely to the mucosal injury. The highest optical densities (medium 2.94 ± 1.2, p<0.0001) were measured in the tTg-neo IgA ELISA of patients with Marsh 3c. As a conclusion, it is suggested that tTg-neo IgA/IgG antibodies should be used preferably to closely reflect intestinal damage during screening and diagnosing childhood CD. EMA-IgA, tTg and DGP checks and mTg-neo IgG titers followed the tTg-neo check performance. mTg-neo IgG may present a new serological biomarker for CD.