Diagnostic Challenges in Celiac Disease and the Role of the Tissue Transglutaminase–Neo-Epitope

  title={Diagnostic Challenges in Celiac Disease and the Role of the Tissue Transglutaminase–Neo-Epitope},
  author={Torsten Matthias and Sascha Pfeiffer and Carlo Francesco Selmi and M. Eric Gershwin},
  journal={Clinical Reviews in Allergy \& Immunology},
The diagnosis of celiac disease (CD) remains a clinical challenge based on the incomplete specificity and sensitivity rates of current non-invasive tests. Furthermore, histological assessments fail to identify all overt cases and, in particular, do not manifest pathognomonic alterations in silent cases. Accordingly, the majority of CD cases are diagnosed with great delay. Recent research into the pathogenesis of CD, allowed us to identify a neo-antigen that appears to be the most promising… 
Serologic Diagnosis of Celiac Disease: New Biomarkers.
Assessment of a Test for the Screening and Diagnosis of Celiac Disease
This study investigates the performance of an ELISA that uses the purified cross‐linked complex of tissue transglutaminase and gliadin, referred as the “neoepitope” (AESKULISA® tTG New Generation), as antigen.
Novel trends in celiac disease
These celiac neo-epitopes are comprised of a complex of gliadin peptides crosslinked with transglutaminase (tTg) and are an early diagnostic marker for CD which occurs up to 6 months earlier than classical markers known to miss a certain amount of CD patients.
Serological Diagnosis of Celiac Disease –Moving Beyond the Tip of the Iceberg
At present, there is insufficient information to demonstrate that screening general populations definitely results in clinical benefit, however, asymptomatic individuals in high-prevalence groups should be screened.
Cutting-Edge Issues in Celiac Disease and in Gluten Intolerance
Some relevant aspects related to the laboratory diagnosis of CD and, more extensively, of gluten intolerance are considered, such as the best combination of tests for early and accurate diagnosis, the diagnostic role of new tests for detecting antibodies against neoepitopes produced by the transglutaminase–gliadin complex, the forms of non-celiac gluten intolerance (gluten sensitivity), and the use and significance of measuring cytokines in CD.
Serological Markers and/or Intestinal Biopsies in the Case-finding of Celiac Disease
Until recent observations are implemented in the future guidelines, small bowel histology should remain the gold standard for case-finding in CD.
Digesting all the options: Laboratory testing for celiac disease
The analytical methodology, strengths, weaknesses, diagnostic performance and clinical utility of the various laboratory tests for celiac disease are reviewed.
A Novel Algorithm for the Diagnosis of Celiac Disease and a Comprehensive Review of Celiac Disease Diagnostics
Using a combination of a sensitive assay together with specific assays improved celiac disease detection rates, with an acceptable number of false positive results, which needs to be confirmed prospectively in both children and adults.
Synthetic Neoepitopes of the Transglutaminase-Deamidated Gliadin Complex as Biomarkers for Diagnosing and Monitoring Celiac Disease.
This work identified immunogenic epitopes of the tTG-DGP complex, and found that an assay to measure the immune response to epitopes accurately identified patients with CeD, as well as patients with mucosal healing.
Comparison of the Reliability of 17 Celiac Disease Associated Bio-Markers to Reflect Intestinal Damage
It is suggested that tTg-neo IgA/IgG antibodies should be used preferably to closely reflect intestinal damage during screening and diagnosing childhood CD.


The pathogenesis of coeliac disease.
Current concepts of celiac disease pathogenesis.
Our knowledge of celiac disease pathogenesis has recently made rapid progress. The disorder is now considered the result of a complex interplay of intrinsic (genetic) and variable extrinsic
IgA anti-tissue transglutaminase: setting the stage for coeliac disease screening
  • D. SchuppanE. Hahn
  • Medicine, Biology
    European journal of gastroenterology & hepatology
  • 2001
A validated and standardized enzyme-linked immunosorbent assay for serum IgA autoantibodies to tissue transglutaminase is a powerful non-invasive test for coeliac disease that promises a sensitivity and specificity close to 100%.
Pathomechanisms in Celiac Disease
Modification of gluten peptides by tTG can enhance their binding to HLA-DQ2 or -DQ8 and potentiate T cell stimulation, and tTG-catalyzed cross-linking and consequent haptenization of gluten with extracellular matrix proteins allows for storage and extended availability of gluten in the mucosa.
Combination testing for antibodies in the diagnosis of coeliac disease: comparison of multiplex immunoassay and ELISA methods
Multiplex immunoassay (MIA) measures multiple antibodies simultaneously providing a complete antibody phenotype with reduced turnaround time and cost.
Extraintestinal manifestations of celiac disease
Overall, autoimmune diseases occur more frequently in those with celiac disease than in the general population, although its effect on some of the extraintestinal manifestations remains to be determined.
Coeliac Disease Gliadin is a Good Substrate of Several Transglutaminases: Possible Implication in the Pathogenesis of Coeliac Disease
Gliadin is a good substrate for endogenous, microbial and plant transglutaminases, and an interesting alternative is that gliadins are deamidated by microbial or food transglUTaminases in the intestinal lumen.
Coeliac disease
Gliadin and tissue transglutaminase complexes in normal and coeliac duodenal mucosa
It is demonstrated that gliadin was directly bound to tTG in duodenal mucosa of coeliacs and controls, and the ability of circulating tTG‐autoantibodies to recognize and immunoprecipitate the t TG‐gliadin complexes is demonstrated.
Coeliac disease: against the grain
  • G. Reeves
  • Medicine
    Internal medicine journal
  • 2004
Coeliac disease is a fascinating hybrid condition, featuring aspects of dietary intolerance and autoimmunity, and presents with malabsorption characterized by weight loss, abdominal distension, diarrhoea and steatorrhoea.