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

Background: 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. Objectives: To investigate the significance of these findings in a well-defined patient cohort. Methods: 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. Results: 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. Conclusion: 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.