Diagnostic performance of three serologic tests in childhood celiac disease

Abstract

Background: IgA- and IgG-antibodies against deamidated gliadin peptides (DGP) specifically bind the disease-inducing antigen and might be superior to transglutaminase type 2 (TG2) IgA in monitoring patients on a gluten-free diet (GFD). The aim of this study was to compare the performance of DGP-IgG and DGP-IgA with TG2-IgA of four manufacturers in pediatric celiac patients at diagnosis and during follow-up under a GFD.

Patients and Methods: In total 411 sera of 91 IgA competent children with biopsy proven celiac disease were analyzed at diagnosis and during follow-up on a GFD. Ninety-eight children with normal duodenal histology served as controls. The tests (TheBindingSite, Euroimmun, Phadia, part of Thermo Fisher Scientific, INOVA) for detection of TG2-IgA, DGP-IgG and DGP-IgA were used according to the manufacturers’ instructions.

Results: Sensitivity to diagnose CD was high for TG2-IgA (100 %) and DGP-IgG (90 − 100 %), but lower for DGP-IgA (67 − 86 %). Specificity was high for all tests (97 – 100 %). The frequency of TG2-IgA titers > 10 × upper limit of normal at diagnosis ranged from 47 − 90 %. Under a GFD DGP-IgA became negative more rapidly than DGP-IgG and TG2-IgA. Non-adherence to GFD was best indicated by positive TG2-IgA.

Conclusions: 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. There are significant differences with respect to proportions of celiac children with titers > 10 × ULN between the manufacturers. This calls for harmonization of tests. TG2-IgA showed the highest titer rise with non-adherence to the GFD, independent of the manufacturer.

Zusammenfassung

Hintergrund: IgA- und IgG-Antikörper gegen deaminierte Gliadin-Peptide (DGP) binden das krankheitsauslösende Antigen und könnten deshalb bei Patienten mit Zöliakie besser zur Verlaufskontrolle unter Gluten-freier Diät (GFD) geeignet sein als Gewebs-Transglutaminase 2 (TG2)-IgA. Ziel dieser Studie war der Vergleich von DGP-IgG und DGP-IgA mit TG2-IgA 4 verschiedener Hersteller zur Diagnostik und Verlaufskontrolle von Kindern mit Zöliakie.

Patienten und Methodik: Es wurden 411 Seren von 91 IgA-kompetenten Kindern mit Biopsie-gesicherter Zöliakie zum Zeitpunkt der Diagnosestellung sowie unter GFD untersucht und mit Seren von 98 Kontrollpatienten verglichen. Die Tests (TheBindingSite, Euroimmun, Phadia/Thermo Fisher Scientific, INOVA) zur Detektion von TG2-IgA, DGP-IgG und DGP-IgA wurden entsprechend der Herstellerangaben durchgeführt.

Ergebnisse: TG2-IgA und DGP-IgG hatten eine signifikant höhere Sensitivität (100 % und 90 − 100 %) für die Diagnose Zöliakie als DGP-IgA (67 − 86 %). Alle Tests hatten eine vergleichbar hohe Spezifität (97 – 100 %). Die Häufigkeit von TG2-IgA > 10 × des oberen Normwerts (ULN) zum Zeitpunkt der Diagnosestellung lag zwischen 47 und 90 %. Unter GFD normalisierte sich DGP-IgA früher als DGP-IgG und TG2-IgA. Bei Diätfehlern hatten TG2-IgA die deutlichsten Titeranstiege.

Schlussfolgerung: Die kombinierte Messung von TG2-IgA und DGP-IgG hat im Vergleich zur alleinigen Bestimmung von TG2-IgA bei IgA-kompetenten Kindern mit Zöliakie keinen diagnostischen Vorteil. Die hohe Variabilität der TG2-IgA > 10 × ULN zeigt, dass eine Harmonisierung der kommerziellen Tests anzustreben ist. Diätfehler unter GFD werden am besten durch einen Anstieg der TG2-IgA diagnostiziert.

Schlüsselwörter

Sprue - Nahrungsmittelintoleranz - Malabsorption - anti-deaminierte Gliadin-Peptide - anti-Gewebs-Transglutaminase 2 - Gluten-freie Diät

Key words

celiac disease - food intolerance - malabsorption - anti-deamidated gliadinpeptide antibody - anti-tissue transglutaminase 2 - gluten-free diet (GFD)

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