Antibodies to wheat high-molecular-weight glutenin subunits in patients with celiac disease

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

Research output: Contribution to journalArticlepeer-review

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-GS-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.

Original languageEnglish
Pages (from-to)428-434
Number of pages7
JournalInternational Archives of Allergy and Immunology
Volume159
Issue number4
DOIs
Publication statusPublished - Nov 2012

Keywords

  • Celiac disease
  • Deamidation
  • Glutenin
  • Screening
  • Wheat gluten

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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