Low positive and borderline negative transglutaminase antibody levels are frequently associated with a coeliac disease diagnosis

TL;DR

Low and borderline transglutaminase antibody levels often indicate coeliac disease, especially when combined with other markers like EmA.

Contribution

The study clarifies the clinical significance of low and borderline TGA levels in diagnosing coeliac disease.

Findings

Low positive TGA values are frequently associated with coeliac disease diagnosis.

Borderline negative TGA values may indicate early-stage coeliac disease.

EmA positivity strongly correlates with coeliac disease in these TGA ranges.

Abstract

Due to the expanding screening of coeliac disease (CeD), low positive and borderline negative serum transglutaminase 2 antibody (TGA) values are causing increasing confusion in clinical practice.

To investigate the significance of these findings in a well‐defined patient cohort.

Altogether 311 IgA‐competent adults, with clinical suspicion or family history of CeD, underwent duodenal sampling and testing for TGA (ImmunoCAP EliA, cut‐off 7.0 U/mL) and endomysial antibodies (EmA). TGA values 7.0–14.0 U/mL were defined as low positive and 3.0–6.9 U/mL as borderline negative. Besides conventional histology, small bowel mucosal TGA‐targeted IgA deposits and γδ+ intraepithelial lymphocytes (IELs) were determined as CeD‐specific markers.

Twenty‐eight (9%) individuals had low positive TGA, and 22 (79%) were also positive for EmA. Among those with low positive TGA, all EmA positive and 50% of the EmA negative subjects were diagnosed with CeD. Thirty‐nine individuals (13%) had borderline negative TGA, and 36% were positive for EmA. Of these, 79% of EmA positive and 12% of EmA negative subjects were diagnosed with CeD. Additionally, 29% of the subjects with borderline negative TGA and no diagnosis exhibited signs of incipient CeD, including positive IgA deposits, increased density of γδ+ IELs and presence of human leukocyte antigen DQ2/DQ8. All subjects with TGA ≥ 3.2× upper limit of normal (22.4 U/mL) received a CeD diagnosis.

Low positive and borderline negative TGA frequently implies a CeD diagnosis, particularly in EmA positive individuals, or at least may be an indicator of an early stage of the disease.

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