The development and validation of a high-capacity serological assay for celiac disease
Klaasen, Rolf; Warren, David; Iversen, Rasmus; Bolstad, Nils; Andersen, Ina Lervåg; Mjønes, Patricia; Rønne, Elin; Lundin, Knut; Sollid, Ludvig Magne; Ness-Jensen, Eivind
Peer reviewed, Journal article
Published version
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Date
2022Metadata
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- Institutt for klinisk og molekylær medisin [3589]
- Publikasjoner fra CRIStin - NTNU [38672]
- St. Olavs hospital [2582]
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.