Screening Tests Using Serum Tissue Transglutaminase IgA May Facilitate the Identification of Undiagnosed Celiac Disease among Japanese Population

Celiac disease (CD) is a lifelong immune-mediated disorder caused by the ingestion of wheat gluten in genetically susceptible persons. Most cases of CD are atypical and remain undiagnosed, which exposes the individuals to the risk of life-threatening complications. Serologic endomysial and tissue transglutaminase antibody tests are used to screen at-risk individuals, although a firm diagnosis requires demonstration of characteristic histopathologic findings in the small-intestinal mucosa. A gluten challenge, with a repeat biopsy to demonstrate recurrence of histopathologic changes in the intestinal mucosa after the re-introduction of gluten, is considered for those persons in whom diagnosis remains in doubt. In this paper, we review studies that evaluated: (1) the possibility of using oral mucosa for the initial diagnosis of CD or for local gluten challenge; and (2) the possibility of using salivary CD-associated antibodies as screening tests. Our review shows that orally based diagnosis of CD is attractive and promising, although additional evaluations with standardized collection and analysis methods are needed. There is some evidence of a dissociation between systemic and oral mucosal immune responses in CD. The hypothesis that gluten could stimulate naïve lymphocytes directly in the oral cavity would have important implications for the understanding, diagnosis, and management of CD.

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Associated factors for celiac disease, and utility of tissue transglutaminase antibody tests for diagnosis: a matched case-control study

10.21203/rs.3.rs-918587/v1 ◽

2021 ◽

Author(s):

Eman Jafar Al Alawi ◽

Nagarajkumar Yenugadhati ◽

Sundas Javad ◽

Hamdan Al Jahdli ◽

Motasim Badri

Keyword(s):

Celiac Disease ◽

Case Control Study ◽

Tissue Transglutaminase ◽

Public Awareness ◽

Conditional Logistic Regression ◽

Case Control ◽

Screening Tests ◽

Intestinal Biopsy ◽

Awareness Campaigns ◽

Control Study

Abstract Background Prevalence of Celiac disease (CD) increased worldwide in recent decades. Approximately 53% of the 33.4 million Saudi population are genetically susceptible and 1.5% develop CD. This underscores the importance of identification of factors associated with CD and the diagnostic accuracy of CD screening tests. Methods In this case-control study records of patients managed between January 2016 and July 2019 at Gastroenterology Department, King Abdul-Aziz Medical City, Riyadh, Saudi Arabia were reviewed. CD cases with confirmed intestinal biopsy were matched (1:1) by age with biopsy negative controls free of CD. Area under the curve (AUC) for anti-tissue transglutaminase IgA (TTG-IgA) and IgG (TTG-IgG) CD diagnostic tests were calculated and compared. Results The study included 270 cases and 270 controls. Sex distribution was similar in both groups. In a stepwise conditional logistic regression analysis, factors significantly associated with CD were family history (odds ratio (OR)=7.76, 95% confidence interval (CI): 2.26-26.63, P=0.001), Helicobacter pylori infection (OR=1.72, 95% CI: 1.10-2.71, P=0.018), diabetes mellitus (OR=3.37, 95% CI: 1.68-6.74, P=0.001), hypothyroidism (OR=2.46, 95% CI: 1.15-5.28, P=0.02) and respiratory infections (OR=4.89,95% CI 2.26-10.56, P<0.001). AUC for TTG-IgA test was 0.934 and for TTG-IgG was 0.787, P<0.001. The optimal cut-off for TTG-IgA was >=12.7 U/ml, with 89% sensitivity and 86% specificity, and for TTG-IgG was >=3.5 U/ml, with 70% sensitivity and 77% specificity.Conclusion The findings of this study can inform strategies for CD screening and prevention. Public awareness campaigns for CD are urgently needed, particularly, for high-risk groups.

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Tissue transglutaminase, the celiac disease autoantigen, preferentially generates antigenic neoepitopes in γ and γ but not in α gliadins

Gastroenterology ◽

10.1016/s0016-5085(01)83407-7 ◽

2001 ◽

Vol 120 (5) ◽

pp. A684-A684

Author(s):

D TRAPP ◽

W DIETERICH ◽

H WIESER ◽

M LEIDENBERGER ◽

D SEILMEIER ◽

...

Keyword(s):

Celiac Disease ◽

Tissue Transglutaminase

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Diagnostic Accuracy of Serologic Screening Tests for Celiac Disease in Asymptomatic Adults and Children with Type 1 Diabetes

Diabetes ◽

10.2337/db18-1579-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 1579-P

Author(s):

MICHELLE GOULD ◽

FARID H. MAHMUD ◽

ANTOINE B. CLARKE ◽

ESTHER ASSOR ◽

AMISH PARIKH ◽

...

Keyword(s):

Type 1 Diabetes ◽

Celiac Disease ◽

Diagnostic Accuracy ◽

Screening Tests ◽

Adults And Children ◽

Serologic Screening

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Screening for celiac disease using anti-tissue transglutaminase antibody assays in healthy students individuals

Diyala Journal for Pure Science ◽

10.24237/djps.1303.236a ◽

2017 ◽

Vol 13 (3) ◽

pp. 162-169

Author(s):

Braihan Hamdi Hameed ◽

Keyword(s):

Celiac Disease ◽

Tissue Transglutaminase ◽

Antibody Assays

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245 THE ORAL TISSUE TRANSGLUTAMINASE INHIBITOR ZED1227 PREVENTS GLUTEN-INDUCED ENTEROPATHY IN A TRANSGENIC MOUSE MODEL OF CELIAC DISEASE

Gastroenterology ◽

10.1016/s0016-5085(21)00873-8 ◽

2021 ◽

Vol 160 (6) ◽

pp. S-53-S-54

Author(s):

Manuel A. Encalada Ventura ◽

Martin Hils ◽

Bernhard Tewes ◽

Ralf Pasternack ◽

Roland Greinwald ◽

...

Keyword(s):

Celiac Disease ◽

Mouse Model ◽

Transgenic Mouse ◽

Tissue Transglutaminase ◽

Transgenic Mouse Model ◽

Oral Tissue

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Tu1386 Susceptibility for Celiac Disease Based on Tissue Transglutaminase Seroprevalence and HLA Genotype in a Community Study

Gastroenterology ◽

10.1016/s0016-5085(16)33011-6 ◽

2016 ◽

Vol 150 (4) ◽

pp. S891

Author(s):

Michael D. Potter ◽

Gregory Brogan ◽

Marjorie M. Walker ◽

Mark McEvoy ◽

Elizabeth Holliday ◽

...

Keyword(s):

Celiac Disease ◽

Tissue Transglutaminase ◽

Community Study ◽

Hla Genotype

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Effect of Rothia mucilaginosa enzymes on gliadin (gluten) structure, deamidation, and immunogenic epitopes relevant to celiac disease

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00144.2014 ◽

2014 ◽

Vol 307 (8) ◽

pp. G769-G776 ◽

Cited By ~ 14

Author(s):

Na Tian ◽

Guoxian Wei ◽

Detlef Schuppan ◽

Eva J. Helmerhorst

Keyword(s):

Celiac Disease ◽

Tissue Transglutaminase ◽

Mass Difference ◽

Cross Linking ◽

Esi Ms ◽

Rp Hplc ◽

Complementary Approach ◽

Sds Page ◽

Rothia Mucilaginosa ◽

Immunogenic Properties

Rothia mucilaginosa, a natural microbial inhabitant of the oral cavity, cleaves gluten (gliadin) proteins at regions that are resistant to degradation by mammalian enzymes. The aim of this study was to investigate to what extent the R. mucilaginosa cell-associated enzymes abolish gliadin immunogenic properties. Degradation of total gliadins and highly immunogenic gliadin 33-mer or 26-mer peptides was monitored by SDS-PAGE and RP-HPLC, and fragments were sequenced by liquid chromatography and electrospray ionization tandem mass spectrometer (LC-ESI-MS/MS). Peptide deamidation by tissue transglutaminase (TG2), a critical step in rendering the fragments more immunogenic, was assessed by TG2-mediated cross-linking to monodansyl cadaverine (MDC), and by a +1-Da mass difference by LC-ESI-MS. Survival of potential immunogenic gliadin epitopes was determined by use of the R5 antibody-based ELISA. R. mucilaginosa-associated enzymes cleaved gliadins, 33-mer and 26-mer peptides into smaller fragments. TG2-mediated cross-linking showed a perfect inverse relationship with intact 33-mer and 26-mer peptide levels, and major degradation fragments showed a slow rate of MDC cross-linking of 6.18 ± 2.20 AU/min compared with 97.75 ± 10.72 and 84.17 ± 3.25 AU/min for the intact 33-mer and 26-mer, respectively, which was confirmed by reduced TG2-mediated deamidation of the fragments in mass spectrometry. Incubation of gliadins with Rothia cells reduced R5 antibody binding by 20, 82, and 97% after 30 min, 2 h, and 5 h, respectively, which was paralleled by reduced reactivity of enzyme-treated 33-mer and 26-mer peptides in the R5 competitive ELISA. Our broad complementary approach to validate gluten degrading activities qualifies R. mucilaginosa-associated enzymes as promising tools to neutralize T cell immunogenic properties for treatment of celiac disease.

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INCREASED TISSUE TRANSGLUTAMINASE LEVELS ARE ASSOCIATED WITH INCREASED EPILEPTIFORM ACTIVITY IN ELECTROENCEPHALOGRAPHY AMONG PATIENTS WITH CELIAC DISEASE

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032015000400005 ◽

2015 ◽

Vol 52 (4) ◽

pp. 272-277 ◽

Cited By ~ 3

Author(s):

Sedat IŞIKAY ◽

Şamil HIZLI ◽

Serkan ÇOŞKUN ◽

Kutluhan YILMAZ

Keyword(s):

Celiac Disease ◽

Tissue Transglutaminase ◽

Pearson Correlation ◽

Epileptiform Activity ◽

Control Group ◽

Healthy Children ◽

Newly Diagnosed ◽

Laboratory Findings ◽

Significant Difference ◽

Medical Histories

Background - Celiac disease is an autoimmune systemic disorder in genetically predisposed individuals precipitated by gluten ingestion. Objective - In this study, we aimed to determine asymptomatic spike-and-wave findings on electroencephalography in children with celiac disease. Methods - A total of 175 children with the diagnosis of celiac disease (study group) and 99 age- and sex-matched healthy children as controls (control group) were included in the study. In order to determine the effects of gluten free diet on laboratory and electroencephalography findings, the celiac group is further subdivided into two as newly-diagnosed and formerly-diagnosed patients. Medical histories of all children and laboratory findings were all recorded and neurologic statuses were evaluated. All patients underwent a sleep and awake electroencephalography. Results - Among 175 celiac disease patients included in the study, 43 were newly diagnosed while 132 were formerly-diagnosed patients. In electroencephalography evaluation of patients the epileptiform activity was determined in 4 (9.3%) of newly diagnosed and in 2 (1.5%) of formerly diagnosed patients; on the other hand the epileptiform activity was present in only 1 (1.0%) of control cases. There was a statistically significant difference between groups in regards to the presence of epileptiform activity in electroencephalography. Pearson correlation analysis revealed that epileptiform activity in both sleep and awake electroencephalography were positively correlated with tissue transglutaminase levels (P=0.014 and P=0.019, respectively). Conclusion - We have determined an increased epileptiform activity frequency among newly-diagnosed celiac disease patients compared with formerly-diagnosed celiac disease patients and control cases. Moreover the tissue transglutaminase levels were also correlated with the presence of epileptiform activity in electroencephalography. Among newly diagnosed celiac disease patients, clinicians should be aware of this association and be alert about any neurological symptoms.

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Relationships between Clinical Presentation, Serology, Histology, and Duodenal Deposits of Tissue Transglutaminase Antibodies in Pediatric Celiac Disease

Digestive Diseases ◽

10.1159/000490377 ◽

2018 ◽

Vol 36 (5) ◽

pp. 369-376 ◽

Cited By ~ 1

Author(s):

Nurit Loberman-Nachum ◽

Michael Schvimer ◽

Camila Avivi ◽

Iris Barshack ◽

Avishay Lahad ◽

...

Keyword(s):

Celiac Disease ◽

Immunohistochemical Staining ◽

Clinical Presentation ◽

Tissue Transglutaminase ◽

Mucosal Damage ◽

High Serum ◽

Tissue Transglutaminase Antibodies ◽

Antibody Levels ◽

Age Range ◽

Multiple Symptoms

Background: The clinical, histological, and serological spectrum of celiac disease (CD) vary widely. We aimed to examine relationships between symptoms, serum anti-tissue transglutaminase antibodies (tTG) levels, mucosal damage, and mucosal anti-tTG deposits in pediatric CD. Methods: A retrospective single-center, cohort study of children referred for endoscopy with suspected CD during 2011–2014. We retrieved the clinical data, blindly reviewed duodenal biopsies, and performed immunohistochemical staining for anti-tTG deposits. Patients were classified as monosymptomatic or polysymptomatic. Mucosal anti-tTG deposits were classified according to the location of deposits, dominant intensity, maximal intensity, and percentage of stained area. Results: Of 252 patients with confirmed CD, complete data were available for 100: 37 males in the age range 1.3–16.7 with median 4.0 years. Monosymptomatic patients (n = 54) presented at an older age than polysymptomatic patients (1.3–15.5, median 8.1 vs. 1.3–16.7, median 6.3 years, p = 0.026). Marsh 2–3c was more prevalent in polysymptomatic patients (93 vs. 78%, p = 0.028). The intensity of mucosal anti-tTG deposits correlated with serum anti-tTG levels but not with the clinical presentation. Conclusions: Multiple symptoms and high serum anti-tTG antibody levels correlated with mucosal damage in children with CD. The role of immunohistochemical staining for intestinal anti-tTG mucosal deposits in the diagnosis of borderline CD is not yet established.

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