Outside of Normal Limits: False Positive/Negative Anti TG2 Autoantibodies

Abstract

Detection of IgA-transglutaminase2 (TG2) autoantibodies has become the test of choice for the diagnosis and monitoring of celiac disease (CD), and is recommended as the serological 'gold standard' by most of the CD societies. Despite its wide acceptance and reasonable performance, several aspects are problematic and disputed. The normal range levels between positivity and negativity are modified, manufacturers' cut-off levels are extremely variable, far from matching in house determinations, insufficient standardization, inadequate reference protocols and no reliable quality assessment of the ELISA antibody (AB) kits for CD diagnosis and follow-up of dietary adherence. Numerous limitations exist in its detection, diagnosis, and follow-up capacities, resulting in frequent clinical circumstances when professionals encounter false positive and negative situations. The present review updates and discusses these facets and aims to extend our knowledge and help CD associated professionals to use the IgA-TG2 antibodies appropriately. We hope that the content of the review will stimulate the scientific community to explore and better delineate the role and functions of the AB and the industrial manufacturers to improve clinical performance of their diagnostic tests.

Comparison of the Reliability of 17 Celiac Disease Associated Bio-Markers to Reflect Intestinal Damage

“…A recent study from the UK national external quality assessment service center (UK NEQAS) states that not all commercial available IgA-tTg kits are reliable and that the ESPGHAN guidelines are not readily transferable to use in all centers and should not be used in the UK [39]. Interestingly, even in the most recommended autoantibodies for CD diagnosis, multiple false positive and negative exist [40].…”

Antibodies against neo-epitope of microbial and human transglutaminase complexes as biomarkers of childhood celiac disease

“…This is also clearly shown in the new ESPGHAN criteria, published in 2012 [29]. It is noteworthy that, having been on the market for several decades, tTG-IgA has been explored extensively, and increasing numbers of false positive and negative results are being described [30,31]. These constitute some of the reasons for the need to better explore serological biomarkers, prompting the present study to challenge tTG-IgA and DGP antibodies against the two neo-epitope antibodies.…”

Gluten-free Diet - Tough Alley in Torrid Time

“…The following is the summary of limitations that are important to clinicians, laboratory staff, dieticians, researchers and others dealing with gluten-sensitive conditions, concerning IgA-TG2 antibodies [27]: The diversity of available test kits, the discrepancy between selective scientific validation, at the bench or bed environment and the fact that they reflect the activity of reactive but not innate immunity, or the intestinal inflammatory state of the CD intestinal mucosa. Furthermore, their performance is age-dependent, not reliable in monitoring disease activity on GFD in CD treated patients and lack of data on the impact of the serological activities on long-term prognosis, complications, extra-intestinal manifestations or autoimmunity genesis or progression.…”

“…Several authors have raised questions regarding the diagnostic performance of IgA-TG2 antibodies in routine clinical practice. Several strategies have been suggested to improve performance or interpretation of the test, but these have not gained wide laboratory application [27].…”

“…At the end of the day, those limitations, difficulties, discrepancies, drawbacks, confusion, lack of appropriate definitions and standardization, numerous false positive and false negative of the gold standard serological marker [27] and lack of peer reviewed reliable information sources, impact the physician and RDNs relations with the end customers and are potentials for delayed or misdiagnosis, mal treatment and lower GFD compliance. As said, GFD in CD is neither a solved problem nor a "closed case".…”