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

AbstractBACKGROUND:
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.
AuthorsH 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
JournalInternational archives of allergy and immunology (Int Arch Allergy Immunol) Vol. 159 Issue 4 Pg. 428-34 ( 2012) ISSN: 1423-0097 [Electronic] Switzerland
PMID22813868 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 S. Karger AG, Basel.
Chemical References
  • Antibodies
  • Immunoglobulin A
  • Protein Subunits
  • Recombinant Proteins
  • Glutens
  • Gliadin
  • Transglutaminases
  • glutenin
Topics
  • Adaptive Immunity
  • Amino Acid Sequence
  • Antibodies (blood, immunology)
  • Antibody Specificity
  • Celiac Disease (blood, diagnosis, immunology)
  • Gliadin (chemistry, immunology)
  • Glutens (chemistry, immunology)
  • Humans
  • Immunoglobulin A (blood, immunology)
  • Molecular Sequence Data
  • Molecular Weight
  • Protein Subunits (chemistry, immunology)
  • Recombinant Proteins (chemistry, metabolism)
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Transglutaminases (metabolism)
  • Triticum (chemistry, immunology)

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