IgA anti-tissue transglutaminase antibodies and IgG antibodies against deamidated gliadin peptides as predictors of celiac disease

AbstractBackground: Assays for IgG antibodies against deamidated gliadin (IgG-anti-dGli) are comparable in performance with tests detecting IgA antibodies against tissue transglutaminase (IgA-anti-tTG) in diagnosing celiac disease (CD). IgA-anti-tTG are absent in IgA deficiency, a condition often associated with CD. In IgA deficiency, IgG-anti-tTG, which have a lower overall diagnostic accuracy, are routinely measured. We examined whether IgG-anti-dGli would be useful for diagnosing CD in patients with IgA deficiency.Methods: We studied 34 IgA-deficient CD patients, 185 IgA-competent newly diagnosed children with CD, 316 children without CD, 400 adult blood donors, and 6 control IgA-deficient individuals without CD. Anti-dGli and anti-tTG were measured by ELISA, and endomysium antibodies (EmA) were measured by immunofluorescence on monkey esophagus (IgA as well as IgG class for all antibodies). We calculated diagnostic sensitivity (percentage of patients above cutoff with 95% CIs) according to age-specific cutoffs for 95% diagnostic specificity and according to cutoffs proposed by the manufacturer of the assays.Results: No IgA-deficient CD patients were positive for any IgA-based antibody assay. Diagnostic sensitivity of IgG-anti-tTG was 91.2% (95% CI 76.3%–97.7%) according to age-specific cutoffs and 82.4% (66.1%–92.0%) according to manufacturer cutoffs. The diagnostic sensitivity of IgG-EmA was 75.8% (58.8%–87.4%) and the sensitivity of IgG-anti-dGli was 88.2% (72.8%–95.9%) according to both cutoffs.Conclusions: IgG-anti-dGli and IgG-anti-tTG have comparable diagnostic sensitivities for IgA-deficient celiac patients. IgG-anti-dGli may be useful for diagnosing CD in IgA-deficient patients.

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Immunoglobulin G (IgG) Anti-Tissue Transglutaminase Antibodies Used as Markers for IgA-Deficient Celiac Disease Patients

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.12.2.254-258.2005 ◽

2005 ◽

Vol 12 (2) ◽

pp. 254-258 ◽

Cited By ~ 50

Author(s):

Ingrid Dahlbom ◽

Martin Olsson ◽

Nahal Kazemi Forooz ◽

Anders G. Sjöholm ◽

Lennart Truedsson ◽

...

Keyword(s):

Celiac Disease ◽

Tissue Transglutaminase ◽

Immunoglobulin A ◽

Good Alternative ◽

Iga Deficiency ◽

Enzyme Linked Immunosorbent Assay ◽

Screening Methods ◽

Igg Antibodies ◽

Negative Results ◽

Tissue Transglutaminase Antibodies

ABSTRACT The role of immunoglobulin A (IgA) anti-tissue transglutaminase antibodies (IgA-tTG) as predictors of untreated celiac disease (CoD) is well documented, and the presence and levels of these antibodies are most accurately monitored with native or recombinant human antigens. However, IgA-deficient CoD patients are not identified by IgA serology, and conflicting results concerning the diagnostic validity of IgG antibodies against gliadin (IgG-AGA), endomysium (IgG-EmA), and tTG (IgG-tTG) have been reported. The aim of the present study was to evaluate the utility of IgG-tTG for the detection of CoD in IgA-deficient patients. Samples from 115 IgA-deficient and 200 IgA-sufficient subjects were collected and tested for the presence of IgA and IgG antibodies against tTG, EmA, and AGA. Antibodies against tTG were measured by an enzyme-linked immunosorbent assay based on recombinant human tTG, and antibodies against EmA were determined by immunofluorescence. The values for IgG-tTG showed a higher correlation (correlation coefficient [r] = 0.91) with those for IgG-EmA for the IgA-deficient subjects than for the IgA-sufficient subjects (r = 0.88). The overall concordance of the positive and negative results between IgG-tTG and IgG-EmA was 97%, and the IgG-tTG assay discriminated between IgG-EmA-positive and -negative subjects with IgA deficiency at a rate of 100%. Elevated levels of IgG-tTG and IgG-EmA were measured in 70% of the IgA-sufficient subjects. IgG-tTG detection with recombinant human tTG is a good alternative to IgG-EmA detection, and the addition of IgG-tTG assessment to present screening methods may improve the ability to identify IgA-deficient subjects with CoD.

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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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Hemolysis may cause false negative results and underdiagnosis of celiac disease when measuring anti-tissue transglutaminase antibodies in serum by immunoassays

Scandinavian Journal of Clinical and Laboratory Investigation ◽

10.1080/00365513.2018.1472802 ◽

2018 ◽

Vol 78 (5) ◽

pp. 428-429

Author(s):

Freja Eriksen ◽

Jutarat Charoenpatrawut ◽

Sumbul Zaman ◽

Isa Neimann Thomasen ◽

Lise Bathum

Keyword(s):

Celiac Disease ◽

Tissue Transglutaminase ◽

False Negative ◽

Negative Results ◽

False Negative Results ◽

Tissue Transglutaminase Antibodies

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Celiac Disease and Liver Disorders: From Putative Pathogenesis to Clinical Implications

Nutrients ◽

10.3390/nu10070892 ◽

2018 ◽

Vol 10 (7) ◽

pp. 892 ◽

Cited By ~ 11

Author(s):

Iva Hoffmanová ◽

Daniel Sánchez ◽

Ludmila Tučková ◽

Helena Tlaskalová-Hogenová

Keyword(s):

Celiac Disease ◽

Liver Diseases ◽

Tissue Transglutaminase ◽

Intestinal Barrier ◽

Rational Approach ◽

Liver Disorders ◽

Tissue Transglutaminase Antibodies ◽

Elevated Transaminases ◽

Made In

Immunologically mediated liver diseases belong to the common extraintestinal manifestations of celiac disease. We have reviewed the current literature that addresses the association between celiac disease and liver disorders. We searched relevant articles on MEDLINE/PubMed up to 15 June 2018. The objective of the article is to provide a comprehensive and up-to-date review on the latest hypotheses explaining the pathogenetic relationship between celiac disease and liver injury. Besides the involvement of gut–liver axis, tissue transglutaminase antibodies, and impairment of intestinal barrier, we integrate the latest achievements made in elucidation of the role of gut microbiota in celiac disease and liver disorders, that has not yet been sufficiently discussed in the literature in this context. The further objective is to provide a complete clinical overview on the types of liver diseases frequently found in celiac disease. In conclusion, the review highlights the clinical implication, recommend a rational approach for managing elevated transaminases in celiac patients, and underscore the importance of screening for celiac disease in patients with associated liver disease.

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Celiac Disease

Clinical Chemistry ◽

10.1093/clinchem/47.11.2023 ◽

2001 ◽

Vol 47 (11) ◽

pp. 2023-2028 ◽

Cited By ~ 80

Author(s):

Mabel Aleanzi ◽

Ana María Demonte ◽

Cecilia Esper ◽

Silvia Garcilazo ◽

Marta Waggener

Keyword(s):

Celiac Disease ◽

Tissue Transglutaminase ◽

Gluten Free ◽

Antibody Recognition ◽

Modified Peptides ◽

Gliadin Peptides ◽

Circulating Antibodies ◽

Native Peptides ◽

Gliadin Antibody ◽

Circulating Antibody

Abstract Background: Selective deamidation of glutamine residues by tissue transglutaminase (tTG) turns gliadin peptides into stronger activators of T cells from celiac disease (CD) patients. We examined the possibility that these modified peptides could be more specific epitopes for circulating antibodies than are native peptides. Methods: Two native synthetic peptides and their respective modified sequences were used as antigens for ELISA assays: peptide-1, with residues 56–75 of α-type gliadin; and peptide-2, with residues 134–153 of γ-type gliadin. We examined 40 CD patients [31 not being treated with a gluten-free diet (GFD) and 9 being treated with a GFD] and 30 non-CD patients. Results: An enhanced response against deamidated peptides was observed in 4 (IgA) and 22 (IgG) of 31 untreated CD patients for peptide-1 and in 25 (IgA) and 29 (IgG) patients for peptide-2. Higher anti-gliadin antibody and anti-tTG IgA concentrations correlated with increased IgA reactivity to modified peptides. Among the nine treated CD patients, eight also displayed an improved IgG signal for the deamidated sequence. Deamidation of peptides did not increase the reactivity of non-CD sera. Conclusions: Selective deamidation specifically increases circulating antibody recognition of gliadin peptides in CD patients. This suggests that deamidated gliadin peptides are more specific CD B-cell epitopes than native peptides; this finding may be relevant for designing improved diagnostic tests.

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