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

Int Arch Allergy Immunol. 2012;159(4):428-34. doi: 10.1159/000338284. Epub 2012 Jul 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Amino Acid Sequence
  • Antibodies / blood
  • Antibodies / immunology
  • Antibody Specificity
  • Celiac Disease / blood
  • Celiac Disease / diagnosis*
  • Celiac Disease / immunology*
  • Gliadin / chemistry
  • Gliadin / immunology*
  • Glutens / chemistry
  • Glutens / immunology*
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin A / immunology
  • Molecular Sequence Data
  • Molecular Weight
  • Protein Subunits / chemistry
  • Protein Subunits / immunology
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Transglutaminases / metabolism
  • Triticum / chemistry
  • Triticum / immunology*

Substances

  • Antibodies
  • Immunoglobulin A
  • Protein Subunits
  • Recombinant Proteins
  • Glutens
  • Gliadin
  • Transglutaminases
  • glutenin