Antibodies to Wheat High-Molecular-Weight Glutenin Subunits in Patients with Celiac Disease

H. Julia Ellis; Pablo Lozano-Sanchez; Carmen Bermudo Redondo; Tanja Suligoj; Federico Biagi; Paola I. Bianchi; Gino R. Corazza; Annalisa De Silvestri; Enzo Bravi; Ioanis Katakis; Ciara K. O'Sullivan; Paul J. Ciclitira

doi:10.1159/000338284

Antibodies to Wheat High-Molecular-Weight Glutenin Subunits in Patients with Celiac Disease

H. Julia Ellis^*, Pablo Lozano-Sanchez, Carmen Bermudo Redondo, Tanja Suligoj, Federico Biagi, Paola I. Bianchi, Gino R. Corazza, Annalisa De Silvestri, Enzo Bravi, Ioanis Katakis, Ciara K. O'Sullivan, Paul J. Ciclitira

^*Corresponding author for this work

Nutritional Sciences

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

Background: Wheat gluten comprises gliadins and glutenins. The high-molecular-weight (HMW) glutenin subunits (GS)-1Dy10 are toxic for patients with celiac disease (CD). This study aimed to assess whether CD patients mount a serological response to HMW-GS-1Dy10. Methods: Recombinant HMW-GS-1Dy10 was deamidated using human recombinant tissue transglutaminase. MALDI-TOF was performed to compare the level of deamidation of glutamine residues between material before and after treatment. Enzyme-linked immunosorbent assays were developed. Sera from patients with untreated CD and gastrointestinal disease controls were tested and receiver operator characteristics were used to calculate cutoffs. Results: MALDI-TOF revealed a number of fragments matching known HMW-GS-1Dy10 sequences within both the deamidated and non-deamidated material. Evidence of deamidation of glutamine residues was found only within the human transglutaminase-treated material. Patients with untreated CD had significantly increased levels of serum antibodies to HMW-GS-1Dy10 compared to controls. Undeamidated HMW-GS-1Dy10 IgA antibodies had sensitivities and specificities of 72.5 and 78.26%, respectively. Deamidated HMW-G5-1Dy10 IgA antibodies had sensitivities and specificities of 76.8 and 65.2%. Undeamidated HMW-GS-1Dy10 IgG antibodies had sensitivities and specificities of 75.3 and 68.1%. Deamidated HMW-GS-1Dy10 IgG antibodies had sensitivities and specificities of 36.2 and 92.8%. Conclusion: Patients with untreated CD have raised antibody levels to HMW-GS-1Dy10, indicating the participation of these proteins in the adaptive immune response to gluten. Discrimination between CD patients and controls is not enhanced by deamidation of HMW-GS-1Dy10. Thus antibodies to these proteins are not useful markers for CD detection. Copyright (C) 2012 S. Karger AG, Basel

Original language	English
Pages (from-to)	428-434
Number of pages	7
Journal	International Archives of Allergy and Immunology
Volume	159
Issue number	4
DOIs	https://doi.org/10.1159/000338284
Publication status	Published - 2012

Keywords

Celiac disease
Deamidation
Glutenin
Screening
Wheat gluten
TISSUE TRANSGLUTAMINASE
ANTIGLIADIN ANTIBODIES
DEAMIDATION
POPULATION
FRACTIONS
RESPONSES
TOXICITY

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10.1159/000338284

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Ellis, H. J., Lozano-Sanchez, P., Bermudo Redondo, C., Suligoj, T., Biagi, F., Bianchi, P. I., Corazza, G. R., De Silvestri, A., Bravi, E., Katakis, I., O'Sullivan, C. K., & Ciclitira, P. J. (2012). Antibodies to Wheat High-Molecular-Weight Glutenin Subunits in Patients with Celiac Disease. International Archives of Allergy and Immunology, 159(4), 428-434. https://doi.org/10.1159/000338284

@article{22770bce465947c58496541d6597b4ef,

title = "Antibodies to Wheat High-Molecular-Weight Glutenin Subunits in Patients with Celiac Disease",

abstract = "Background: Wheat gluten comprises gliadins and glutenins. The high-molecular-weight (HMW) glutenin subunits (GS)-1Dy10 are toxic for patients with celiac disease (CD). This study aimed to assess whether CD patients mount a serological response to HMW-GS-1Dy10. Methods: Recombinant HMW-GS-1Dy10 was deamidated using human recombinant tissue transglutaminase. MALDI-TOF was performed to compare the level of deamidation of glutamine residues between material before and after treatment. Enzyme-linked immunosorbent assays were developed. Sera from patients with untreated CD and gastrointestinal disease controls were tested and receiver operator characteristics were used to calculate cutoffs. Results: MALDI-TOF revealed a number of fragments matching known HMW-GS-1Dy10 sequences within both the deamidated and non-deamidated material. Evidence of deamidation of glutamine residues was found only within the human transglutaminase-treated material. Patients with untreated CD had significantly increased levels of serum antibodies to HMW-GS-1Dy10 compared to controls. Undeamidated HMW-GS-1Dy10 IgA antibodies had sensitivities and specificities of 72.5 and 78.26%, respectively. Deamidated HMW-G5-1Dy10 IgA antibodies had sensitivities and specificities of 76.8 and 65.2%. Undeamidated HMW-GS-1Dy10 IgG antibodies had sensitivities and specificities of 75.3 and 68.1%. Deamidated HMW-GS-1Dy10 IgG antibodies had sensitivities and specificities of 36.2 and 92.8%. Conclusion: Patients with untreated CD have raised antibody levels to HMW-GS-1Dy10, indicating the participation of these proteins in the adaptive immune response to gluten. Discrimination between CD patients and controls is not enhanced by deamidation of HMW-GS-1Dy10. Thus antibodies to these proteins are not useful markers for CD detection. Copyright (C) 2012 S. Karger AG, Basel",

keywords = "Celiac disease, Deamidation, Glutenin, Screening, Wheat gluten, TISSUE TRANSGLUTAMINASE, ANTIGLIADIN ANTIBODIES, DEAMIDATION, POPULATION, FRACTIONS, RESPONSES, TOXICITY",

author = "Ellis, {H. Julia} and Pablo Lozano-Sanchez and {Bermudo Redondo}, Carmen and Tanja Suligoj and Federico Biagi and Bianchi, {Paola I.} and Corazza, {Gino R.} and {De Silvestri}, Annalisa and Enzo Bravi and Ioanis Katakis and O'Sullivan, {Ciara K.} and Ciclitira, {Paul J.}",

year = "2012",

doi = "10.1159/000338284",

language = "English",

volume = "159",

pages = "428--434",

journal = "International Archives of Allergy and Immunology",

issn = "1018-2438",

publisher = "S. Karger AG",

number = "4",

}

Ellis, HJ, Lozano-Sanchez, P, Bermudo Redondo, C, Suligoj, T, Biagi, F, Bianchi, PI, Corazza, GR, De Silvestri, A, Bravi, E, Katakis, I, O'Sullivan, CK & Ciclitira, PJ 2012, 'Antibodies to Wheat High-Molecular-Weight Glutenin Subunits in Patients with Celiac Disease', International Archives of Allergy and Immunology, vol. 159, no. 4, pp. 428-434. https://doi.org/10.1159/000338284

TY - JOUR

T1 - Antibodies to Wheat High-Molecular-Weight Glutenin Subunits in Patients with Celiac Disease

AU - Ellis, H. Julia

AU - Lozano-Sanchez, Pablo

AU - Bermudo Redondo, Carmen

AU - Suligoj, Tanja

AU - Biagi, Federico

AU - Bianchi, Paola I.

AU - Corazza, Gino R.

AU - De Silvestri, Annalisa

AU - Bravi, Enzo

AU - Katakis, Ioanis

AU - O'Sullivan, Ciara K.

AU - Ciclitira, Paul J.

PY - 2012

Y1 - 2012

N2 - Background: Wheat gluten comprises gliadins and glutenins. The high-molecular-weight (HMW) glutenin subunits (GS)-1Dy10 are toxic for patients with celiac disease (CD). This study aimed to assess whether CD patients mount a serological response to HMW-GS-1Dy10. Methods: Recombinant HMW-GS-1Dy10 was deamidated using human recombinant tissue transglutaminase. MALDI-TOF was performed to compare the level of deamidation of glutamine residues between material before and after treatment. Enzyme-linked immunosorbent assays were developed. Sera from patients with untreated CD and gastrointestinal disease controls were tested and receiver operator characteristics were used to calculate cutoffs. Results: MALDI-TOF revealed a number of fragments matching known HMW-GS-1Dy10 sequences within both the deamidated and non-deamidated material. Evidence of deamidation of glutamine residues was found only within the human transglutaminase-treated material. Patients with untreated CD had significantly increased levels of serum antibodies to HMW-GS-1Dy10 compared to controls. Undeamidated HMW-GS-1Dy10 IgA antibodies had sensitivities and specificities of 72.5 and 78.26%, respectively. Deamidated HMW-G5-1Dy10 IgA antibodies had sensitivities and specificities of 76.8 and 65.2%. Undeamidated HMW-GS-1Dy10 IgG antibodies had sensitivities and specificities of 75.3 and 68.1%. Deamidated HMW-GS-1Dy10 IgG antibodies had sensitivities and specificities of 36.2 and 92.8%. Conclusion: Patients with untreated CD have raised antibody levels to HMW-GS-1Dy10, indicating the participation of these proteins in the adaptive immune response to gluten. Discrimination between CD patients and controls is not enhanced by deamidation of HMW-GS-1Dy10. Thus antibodies to these proteins are not useful markers for CD detection. Copyright (C) 2012 S. Karger AG, Basel

AB - Background: Wheat gluten comprises gliadins and glutenins. The high-molecular-weight (HMW) glutenin subunits (GS)-1Dy10 are toxic for patients with celiac disease (CD). This study aimed to assess whether CD patients mount a serological response to HMW-GS-1Dy10. Methods: Recombinant HMW-GS-1Dy10 was deamidated using human recombinant tissue transglutaminase. MALDI-TOF was performed to compare the level of deamidation of glutamine residues between material before and after treatment. Enzyme-linked immunosorbent assays were developed. Sera from patients with untreated CD and gastrointestinal disease controls were tested and receiver operator characteristics were used to calculate cutoffs. Results: MALDI-TOF revealed a number of fragments matching known HMW-GS-1Dy10 sequences within both the deamidated and non-deamidated material. Evidence of deamidation of glutamine residues was found only within the human transglutaminase-treated material. Patients with untreated CD had significantly increased levels of serum antibodies to HMW-GS-1Dy10 compared to controls. Undeamidated HMW-GS-1Dy10 IgA antibodies had sensitivities and specificities of 72.5 and 78.26%, respectively. Deamidated HMW-G5-1Dy10 IgA antibodies had sensitivities and specificities of 76.8 and 65.2%. Undeamidated HMW-GS-1Dy10 IgG antibodies had sensitivities and specificities of 75.3 and 68.1%. Deamidated HMW-GS-1Dy10 IgG antibodies had sensitivities and specificities of 36.2 and 92.8%. Conclusion: Patients with untreated CD have raised antibody levels to HMW-GS-1Dy10, indicating the participation of these proteins in the adaptive immune response to gluten. Discrimination between CD patients and controls is not enhanced by deamidation of HMW-GS-1Dy10. Thus antibodies to these proteins are not useful markers for CD detection. Copyright (C) 2012 S. Karger AG, Basel

KW - Celiac disease

KW - Deamidation

KW - Glutenin

KW - Screening

KW - Wheat gluten

KW - TISSUE TRANSGLUTAMINASE

KW - ANTIGLIADIN ANTIBODIES

KW - DEAMIDATION

KW - POPULATION

KW - FRACTIONS

KW - RESPONSES

KW - TOXICITY

U2 - 10.1159/000338284

DO - 10.1159/000338284

M3 - Article

SN - 1018-2438

VL - 159

SP - 428

EP - 434

JO - International Archives of Allergy and Immunology

JF - International Archives of Allergy and Immunology

IS - 4

ER -

Antibodies to Wheat High-Molecular-Weight Glutenin Subunits in Patients with Celiac Disease

Abstract

Keywords

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