Limited Efficiency of Prolyl-Endopeptidase in the Detoxification of Gliadin Peptides in Celiac Disease

Celiac disease (CD) is a chronic immune-mediated enteropathy triggered by exposure to dietary gluten in genetically predisposed individuals. In contrast, irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder affecting the large intestine, without an autoimmune component. Here, we evaluated the prevalence of IgA and IgG antibodies to maize zeins (AZA) in patients with CD and IBS. Using an in-house ELISA assay, the IgA and IgG anti-zein antibodies in the serum of 37 newly diagnosed CD (16 biopsy proved and 21 serological diagnosis) and 375 IBS patients or 302 healthy control (HC) subjects were measured. Elevated levels of IgA AZA were found in CD patients compared with IBS patients (p < 0.01) and HC (p < 0.05). CD patients had the highest prevalence (35.1%), followed by IBS (4.3%) and HCs (2.3%) (p < 0.0001). IgG AZA antibodies were not found in any CD patients, IBS patients, or HC subjects. A significant positive correlation was found between IgA AZA with IgA anti-gliadin (AGA, r = 0.34, p < 0.01) and IgA anti-deaminated gliadin peptides (DGP, r = 0.42, p < 0.001) in the celiac disease group. Taken together, our results show for the first time a higher prevalence of AZA IgA antibodies in newly diagnosed CD patients than in IBS patients, confirming a biased immune response to other gliadin-related prolamins such as maize zeins in genetically susceptible individuals.

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Evaluation of the INOVA Diagnostics Enzyme-Linked Immunosorbent Assay Kits for Measuring Serum Immunoglobulin G (IgG) and IgA to Deamidated Gliadin Peptides

Clinical and Vaccine Immunology ◽

10.1128/cvi.13.1.150-151.2006 ◽

2006 ◽

Vol 13 (1) ◽

pp. 150-151 ◽

Cited By ~ 44

Author(s):

Harry E. Prince

Keyword(s):

Celiac Disease ◽

Immunosorbent Assay ◽

Immunoglobulin G ◽

Immunoglobulin A ◽

Serum Immunoglobulin ◽

Enzyme Linked Immunosorbent Assay ◽

Gliadin Antibodies ◽

Gliadin Peptides ◽

Disease Specific ◽

Inova Diagnostics

ABSTRACT New assays for antibodies to deamidated gliadin peptides (DGP) expressing celiac disease-specific epitopes were evaluated using 154 sera previously tested for endomysial immunoglobulin A (IgA) (EMA), transglutaminase IgA (TGA), and conventional gliadin antibodies. DGP antibody results showed 97% concordance with EMA and TGA results. Of 56 sera negative for EMA and TGA but positive for conventional gliadin antibodies, 54 (96%) were negative for DGP antibodies.

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Targeting of gliadin peptides, CD8, α/β‐TCR, and γ/δ‐TCR to Golgi complexes and vacuoles within celiac disease enterocytes

The FASEB Journal ◽

10.1096/fasebj.12.13.1349 ◽

1998 ◽

Vol 12 (13) ◽

pp. 1349-1357 ◽

Cited By ~ 20

Author(s):

Klaus‐Peter Zimmer ◽

Hassan Naim ◽

Peter Weber ◽

H. Julia Ellis ◽

Paul J. Ciclitira

Keyword(s):

Celiac Disease ◽

Gliadin Peptides

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Biased T Cell Receptor Usage Directed against Human Leukocyte Antigen DQ8-Restricted Gliadin Peptides Is Associated with Celiac Disease

Immunity ◽

10.1016/j.immuni.2012.07.013 ◽

2012 ◽

Vol 37 (4) ◽

pp. 611-621 ◽

Cited By ~ 80

Author(s):

Sophie E. Broughton ◽

Jan Petersen ◽

Alex Theodossis ◽

Stephen W. Scally ◽

Khai Lee Loh ◽

...

Keyword(s):

Celiac Disease ◽

T Cell ◽

Human Leukocyte Antigen ◽

T Cell Receptor ◽

Human Leukocyte ◽

Cell Receptor ◽

Leukocyte Antigen ◽

Receptor Usage ◽

Gliadin Peptides

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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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Sa1290 Utilizing High Throughput Discovery Approach to Identify Optimal Candidate Deamidated Gliadin Peptides for the Identification of Celiac Disease.

Gastroenterology ◽

10.1016/s0016-5085(13)60896-3 ◽

2013 ◽

Vol 144 (5) ◽

pp. S-253

Author(s):

Joseph A. Murray ◽

Melissa Snyder ◽

Carol T. Van Dyke ◽

Tricia L. Brantner ◽

Vasanth Jayaraman ◽

...

Keyword(s):

Celiac Disease ◽

High Throughput ◽

Gliadin Peptides ◽

Optimal Candidate

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Antibodies against Synthetic Deamidated Gliadin Peptides for Celiac Disease Diagnosis and Follow-Up in Children

Clinical Chemistry ◽

10.1373/clinchem.2008.110395 ◽

2009 ◽

Vol 55 (1) ◽

pp. 150-157 ◽

Cited By ~ 59

Author(s):

Daniela Basso ◽

Graziella Guariso ◽

Paola Fogar ◽

Alessandra Meneghel ◽

Carlo-Federico Zambon ◽

...

Keyword(s):

Celiac Disease ◽

Predictive Value ◽

Disease Diagnosis ◽

Iga Deficiency ◽

Serum Markers ◽

Gluten Free Diet ◽

Gluten Free ◽

Gliadin Peptides ◽

Celiac Disease Diagnosis ◽

Cd Marker

AbstractBackground: AGA IgA II and AGA IgG II have recently been suggested as reliable tools for celiac disease (CD) diagnosis. We compared their utility for diagnosis and monitoring CD in children with that of tTG IgA, an established CD marker.Methods: We studied a cohort of 161 CD and 129 control children in whom CD was histologically confirmed or ruled out. We followed 37 children with CD on a gluten-free diet for 12–84 months. In fasting sera, we measured AGA IgA II, AGA IgG II, and tTG IgA using ELISAs.Results: The best sensitivity (92.5%), specificity (97.6%), positive predictive value (98%), and negative predictive value (91.2%) were obtained using tTG IgA. AGA IgG II correctly identified 3 of 3 children with CD with total IgA deficiency who had negative AGA IgA II and tTG IgA results. In children <2 years old without total IgA deficiency, AGA IgG II and tTG IgA performed equally well (sensitivity 96.4% and specificity 100%). AGA IgA II, AGA IgG II, and tTG IgA concentrations diminished significantly (P < 0.0001) after 1 year of a gluten-free diet, reaching values below the cutoff in 87%, 70%, and 51% of cases, respectively.Conclusions: The best available index for diagnosing CD in children was tTG IgA. In infants <2 years old, AGA IgG II performed as well as tTG IgA in cases without total IgA deficiency and allowed detection of CD when total IgA was <0.06 g/L. Gluten-free diet monitoring can be achieved using any of the studied serum markers.

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A new microbial gluten-degrading prolyl endopeptidase: Potential application in celiac disease to reduce gluten immunogenic peptides

PLoS ONE ◽

10.1371/journal.pone.0218346 ◽

2019 ◽

Vol 14 (6) ◽

pp. e0218346 ◽

Cited By ~ 3

Author(s):

María de Lourdes Moreno Amador ◽

Miguel Arévalo-Rodríguez ◽

Encarnación Mellado Durán ◽

Juan Carlos Martínez Reyes ◽

Carolina Sousa Martín

Keyword(s):

Celiac Disease ◽

Potential Application ◽

Prolyl Endopeptidase ◽

Immunogenic Peptides

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IgG Antibodies against Deamidated Gliadin Peptides for Diagnosis of Celiac Disease in Patients with IgA Deficiency

Clinical Chemistry ◽

10.1373/clinchem.2009.128132 ◽

2010 ◽

Vol 56 (3) ◽

pp. 464-468 ◽

Cited By ~ 60

Author(s):

Danilo Villalta ◽

Elio Tonutti ◽

Christian Prause ◽

Sibylle Koletzko ◽

H Holm Uhlig ◽

...

Keyword(s):

Celiac Disease ◽

Blood Donors ◽

Tissue Transglutaminase ◽

Iga Deficiency ◽

Diagnostic Sensitivity ◽

Igg Antibodies ◽

Diagnostic Specificity ◽

Gliadin Peptides ◽

Endomysium Antibodies ◽

Monkey Esophagus

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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