Detection of specific IgA antibodies against a novel deamidated 8-Mer gliadin peptide in blood plasma samples from celiac patients

PLoS One. 2013 Nov 22;8(11):e80982. doi: 10.1371/journal.pone.0080982. eCollection 2013.

Abstract

We studied whether celiac disease (CD) patients produce antibodies against a novel gliadin peptide specifically generated in the duodenum of CD patients by a previously described pattern of CD-specific duodenal proteases. Fingerprinting and ion-trap mass spectrometry of CD-specific duodenal gliadin-degrading protease pattern revealed a new 8-mer gliadin-derived peptide. An ELISA against synthetic deamidated 8-mer peptides (DGP 8-mer) was used to study the presence of IgA anti-DGP 8-mer antibodies in plasma samples from 81 children (31 active CD patients (aCD), 17 CD patients on a gluten-free diet (GFD), 10 healthy controls (C) and 23 patients with other gastrointestinal pathology (GP)) and 101 adults (16 aCD, 12 GFD, 27 C and 46 GP-patients). Deamidation of the 8-mer peptide significantly increased the reactivity of the IgA antibodies from CD patients against the peptide. Significant IgA anti-DGP 8-mer antibodies levels were detected in 93.5% of aCD-, 11.8% of GFD- and 4.3% of GP-patients in children. In adults, antibodies were detected in 81.3% of aCD-patients and 8.3% of GFD-patients while were absent in 100% of C- and GP-patients. Duodenal CD-specific gliadin degrading proteases release an 8-mer gliadin peptide that once deamidated is an antigen for specific IgA antibodies in CD patients which may provide a new accurate diagnostic tool in CD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Antibody Specificity / immunology*
  • Celiac Disease / genetics
  • Celiac Disease / immunology*
  • Celiac Disease / metabolism
  • Celiac Disease / pathology
  • Child
  • Child, Preschool
  • Duodenum / immunology
  • Duodenum / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Gliadin / chemistry
  • Gliadin / immunology*
  • Gliadin / metabolism
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin A / immunology*
  • Infant
  • Male
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology*
  • Peptide Hydrolases / metabolism
  • Proteolysis

Substances

  • Epitopes, T-Lymphocyte
  • Immunoglobulin A
  • Peptide Fragments
  • Gliadin
  • Peptide Hydrolases

Grant support

This work has been supported by grants (to EA) from the Instituto de Salud Carlos III – FEDER (PI070244, PI10/01647), Junta de Castilla y León (SAN126/VA31/09), AECID (A/019196/08), and Phadia Spain S.L (now ThermoFisher Scientific). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.