The development and validation of a high-capacity serological assay for celiac disease.

Abstract

BACKGROUND:

The aim of the present study was to develop and clinically validate a high-throughput assay for serum IgA and IgG antibodies against transglutaminase-2 (TG2) and to determine appropriate assay cut-offs for large-scale population screening for celiac disease.

METHOD:

An automated method was developed using dual label time-resolved fluorometry on the AutoDELFIA platform. Individuals (n = 1920) from the general population were screened. Subjects with serum anti-TG2 concentrations above a preliminary cut-off (>0.3 mg*/L anti-TG2 IgA or >0.5 mg*/L anti-TG2 IgG) were offered endoscopic examination and biopsy. A diagnosis of celiac disease was given if villous atrophy (Marsh grade 3) was found.

RESULTS:

The assay had a limit of quantification of 0.25 mg*/L (anti-TG2 IgA) and 0.60 mg*/L (anti-TG2 IgG) with imprecision (CV) < 16% and <18% respectively. A total of 66 individuals were above the preliminary cut-off, and 56 underwent endoscopy. Of these, 26 were diagnosed with celiac disease. Sixty-eight percent of subjects with anti-TG2 IgA ≥ 0.7 mg*/L or anti-TG2 IgG ≥ 1.0 mg*/L had biopsy-proven celiac disease, and utilization of these higher cut-offs identified 96% of biopsy-positive patients. At the time of endoscopy, all individuals with anti-TG2 IgA > 2.0 mg*/L had celiac disease, and this cut-off identified 88% of newly diagnosed celiac patients. Eight percent (2/26) of the newly diagnosed patients had primarily anti-TG2 IgG.

CONCLUSIONS:

In this study we developed and clinically validated a robust and automated assay suitable for celiac disease screening in the general population.

• Authors: Rolf A Klaasen, David J Warren, Rasmus Iversen, Nils Bolstad, Ina L Andersen, Patricia Mjønes, Elin Rønne, Knut E A Lundin, Ludvig M Sollid, Eivind Ness-Jensen
• Journal: Clinical biochemistry (Clin Biochem) Vol. 107 Pg. 13-18 (Sep 2022) ISSN: 1873-2933 [Electronic] United States
• PMID: 35660483 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Autoantibodies
• Immunoglobulin A
• Immunoglobulin G
• Protein Glutamine gamma Glutamyltransferase 2
• Transglutaminases
• GTP-Binding Proteins

Topics

• Autoantibodies
• Biopsy
• Celiac Disease (diagnosis)
• GTP-Binding Proteins
• Humans
• Immunoglobulin A
• Immunoglobulin G
• Protein Glutamine gamma Glutamyltransferase 2
• Transglutaminases