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

Lerner, Aaron; Jeremias, Patricia; Neidhöfer, ra; Tenbusch, Matthias

doi:10.4172/2155-9899.1000486

Cited by 14 publications

(20 citation statements)

References 41 publications

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“…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. The present results reinforce the findings of comparable studies, where tTG–IgA and tTG‐neo were compared back‐to‐back for CD diagnosis , and tTG‐neo was found to outperform tTG‐IgA in CD .…”

Section: Discussionsupporting

confidence: 90%

“…In summary, comparing IgA, IgG and IgA + IgG (check) isotypes of tTG, tTG-neo, mTG-neo and DGP check, the tTG-neo check stood out as the most effective biomarker for CD diagnosis and intestinal damage reflection. Based on the present and published data [14,32,33], it is suggested that the serological marker of tTG-neo check antibodies should be recommended as a first-line diagnostic screening test for CD in children. The tTG and tTG-neo IgA assays show similar diagnostic performance, and are both recommended as good screening tests for CD in children.…”

Section: Discussionmentioning

confidence: 95%

“…Complexed to gliadin, mTG shows an enhanced immunogenicity in children with CD, and anti‐mTG‐neo‐epitope IgG antibodies correlate with intestinal damage to a comparable degree to anti‐tTG‐neo IgA . Additionally, mTG and tTG displayed a comparable immunopotent epitope despite the fact that they do not share sequence homology .…”

Section: Discussionmentioning

confidence: 99%

“…Complexed to gliadin, mTG shows an enhanced immunogenicity in children with CD, and anti-mTG-neo-epitope IgG antibodies correlate with intestinal damage to a comparable degree to anti-tTG-neo IgA [14,32]. Additionally, mTG and tTG displayed a comparable immunopotent epitope despite the fact that they do not share sequence homology [14,32]. In summary, mTG-neo IgG presents a new marker for CD, and further studies are needed to explore the pathogenic potential of anti-mTG antibodies in CD involvement.…”

Section: Discussionmentioning

confidence: 99%

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

Agardh

Tenbusch²,

Wusterhausen³

et al. 2019

Clinical and Experimental Immunology

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Summary Tissue transglutaminase (tTG) and microbial transglutaminase (mTG) cross‐link gliadins to form complexes that expose immunogenic neo‐epitopes to produce tTG and mTG‐neo‐epitope antibodies. The aim of this study was to test the diagnostic performance of antibodies against non‐complexed and complexed forms of transglutaminases, to correlate their activities to the intestinal damage and to explore age group dependency in celiac disease (CD). A total of 296 children with untreated CD and 215 non‐celiac disease controls were checked by in‐house enzyme‐linked immunosorbent assays detecting immunoglobulin (Ig)A, IgG or combined detection of IgA and IgG (check) against tTG, AESKULISA® tTG New Generation (tTG‐neo) and mTG‐neo (RUO), IgA and IgG antibodies against deamidated gliadin peptide (DGP) and human IgA anti‐endomysium antibodies (EMA) using AESKUSLIDES® EMA. Intestinal pathology was graded according the revised Marsh criteria, and age dependencies of the antibody activities were analysed. Using cut‐offs estimated from receiver operating characteristic (ROC) curves, the highest area under curve (AUC) of the TG assays was 0·963 for tTG‐neo check, followed by tTG check (0·962) when the diagnosis was based on enteric mucosal histology. tTG‐neo check was the most effective to reflect the intestinal abnormalities in CD (r = 0·795, P < 0·0001). High levels of anti‐mTG‐neo IgG and anti‐tTG‐neo IgG appeared in the earlier age groups, as compared to anti‐tTG IgG (P < 0·001). Considering antibody diagnostic performance based on AUC, enteric damage reflection and predictability at an early age, the anti‐neo tTG check was the most effective diagnostic biomarker for pediatric CD. The mTG neo check might represent a new marker for CD screening, diagnosis and predictability.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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

Agardh

Tenbusch²,

Wusterhausen³

et al. 2019

Clinical and Experimental Immunology

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“…The transition from naive antigens to foreign ones represents a loss of tolerance, resulting in reactive immune stimulation and the generation of a new family of antibodies, namely, neo-epitope antibodies. Neo-epitope tTG (tTG neo) [14,25,[51][52][53][54][55] and neo-epitope mTG (mTG-neo) antibodies [7,13,14,25,[51][52][53][54]56,57] appear in the systemic circulation. The present review will concentrate on the immunogenicity of the mTG-gliadin cross-linked complexes, mTG-neo antibodies in CD.…”

Section: Microbial Transglutaminase-gliadin Cross-linked Complexes Armentioning

confidence: 99%

Processed Food Additive Microbial Transglutaminase and Its Cross-Linked Gliadin Complexes Are Potential Public Health Concerns in Celiac Disease

Lerner¹,

Tenbusch²

2020

IJMS

Self Cite

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Microbial transglutaminase (mTG) is a survival factor for microbes, but yeasts, fungi, and plants also produce transglutaminase. mTG is a cross-linker that is heavily consumed as a protein glue in multiple processed food industries. According to the manufacturers' claims, microbial transglutaminase and its cross-linked products are safe, i.e., nonallergenic, nonimmunogenic, and nonpathogenic. The regulatory authorities declare it as "generally recognized as safe" for public users. However, scientific observations are accumulating concerning its undesirable effects on human health. Functionally, mTG imitates its family member, tissue transglutaminase, which is the autoantigen of celiac disease. Both these transglutaminases mediate cross-linked complexes, which are immunogenic in celiac patients. The enzyme enhances intestinal permeability, suppresses mechanical (mucus) and immunological (anti phagocytic) enteric protective barriers, stimulates luminal bacterial growth, and augments the uptake of gliadin peptide. mTG and gliadin molecules are cotranscytosed through the enterocytes and deposited subepithelially. Moreover, mucosal dendritic cell surface transglutaminase induces gliadin endocytosis, and the enzyme-treated wheat products are immunoreactive in CD patients. The present review summarizes and updates the potentially detrimental effects of mTG, aiming to stimulate scientific and regulatory debates on its safety, to protect the public from the enzyme's unwanted effects.

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Commonly Used Food Additives Are Nutritional Adjuvants in ASIA Syndrome

Lerner,

Benzvi

2024

Autoimmune Disorders

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

Cited by 14 publications

References 41 publications

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

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

Processed Food Additive Microbial Transglutaminase and Its Cross-Linked Gliadin Complexes Are Potential Public Health Concerns in Celiac Disease

Commonly Used Food Additives Are Nutritional Adjuvants in ASIA Syndrome

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