Introduction
Coeliac disease (CD) is an immune-mediated disorder of the small intestine triggered by dietary gluten. The diagnosis is based on serological testing and histological examination. Selective immunoglobulin (Ig) A deficiency is a more common condition amongst CD patients than in the general population, complicating the use of IgA antibodies to diagnose CD. Current guidelines suggest testing for the level of total immunoglobulin A (IgA) and the level of specific anti-transglutaminase 2 (TG2) IgA in the search for CD. Only when severe IgA deficiency is found, immunoglobulin G (IgG) based testing is recommended. In a pilot study for validating a dual TG2 IgA/IgG screening assay, we found CD patients primarily responding with TG2 IgG antibodies and not TG2 IgA, despite IgA sufficiency (1). Thus, these patients risk never being diagnosed.
Aims & Methods
The aim of this study was to assess the additional benefit of testing for TG2 IgG alongside TG2 IgA in screening for CD in adults. The study was based on the fourth Trøndelag Health Study (HUNT4), a population-based study of 56,000 adult (>20 years of age) Norwegians (2). Serum samples were analysed using a combined TG2 IgA and IgG assay and the seropositives were invited to endoscopy with duodenal biopsies for histological confirmation (Marsh grade 3). The prevalence of primary TG2 IgG responders and the positive predictive value (PPV) of TG2 IgG among TG2 IgA negative participants were calculated.
Results
Serum from 54,505 participants were analysed and 1107 were seropositive. The present study included 593 participants with histological examination and CD was confirmed in 403 participants. Primary TG2 IgG response was found in 75 participants, of whom four got CD confirmed. None of these four participants had total IgA deficiency. The PPV of TG2 IgG for CD among TG2 IgA negative participants was 5.3% (95% confidence interval 3.5-7.1). In comparison, the PPV of TG2 IgA was 77.0% (73.6-80.4).
Conclusion
This population-based screening for CD among adults found a small group of individuals with CD that risk not being diagnosed using the current diagnostic guidelines, due to primary TG2 IgG response in the absence of IgA deficiency. However, TG2 IgG is still too unspecific to be used in the screening of CD in the general population.
References
1. Klaasen RA, Warren DJ, Iversen R, Bolstad N, Andersen IL, Mjones P, et al. The development and validation of a high-capacity serological assay for celiac disease. Clin Biochem. 2022;107:13-8.
2. Lukina P, Andersen IL, Eggen PT, Mjones PG, Ronne E, Bolstad N, et al. Coeliac disease in the Trondelag Health Study (HUNT), Norway, a population-based cohort of coeliac disease patients. BMJ Open. 2024;14(1):e077131.
