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Diós Á, Elek R, Szabó I, et al. Gamma-gliadin specific celiac disease antibodies recognize p31-43 and p57-68 alpha gliadin peptides in deamidation related manner as a result of cross-reaction. Amino Acids. 2021;53(7):1051-1063doi: 10.1007/s00726-021-03006-7.
Diós, �. �., Elek, R., Szabó, I., Horváth, S., Gyimesi, J., Király, R., Werkstetter, K., Koletzko, S., Fésüs, L., & Korponay-Szabó, I. R. (2021). Gamma-gliadin specific celiac disease antibodies recognize p31-43 and p57-68 alpha gliadin peptides in deamidation related manner as a result of cross-reaction. Amino acids, 53(7), 1051-1063. https://doi.org/10.1007/s00726-021-03006-7
Diós, Ádám, et al. "Gamma-gliadin specific celiac disease antibodies recognize p31-43 and p57-68 alpha gliadin peptides in deamidation related manner as a result of cross-reaction." Amino acids vol. 53,7 (2021): 1051-1063. doi: https://doi.org/10.1007/s00726-021-03006-7
Diós Á, Elek R, Szabó I, Horváth S, Gyimesi J, Király R, Werkstetter K, Koletzko S, Fésüs L, Korponay-Szabó IR. Gamma-gliadin specific celiac disease antibodies recognize p31-43 and p57-68 alpha gliadin peptides in deamidation related manner as a result of cross-reaction. Amino Acids. 2021 Jul;53(7):1051-1063. doi: 10.1007/s00726-021-03006-7. Epub 2021 May 31. PMID: 34059947; PMCID: PMC8241804.
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Amino Acids. 2021 Jul;53(7):1051-1063. doi: 10.1007/s00726-021-03006-7. Epub 2021 May 31.

Gamma-gliadin specific celiac disease antibodies recognize p31-43 and p57-68 alpha gliadin peptides in deamidation related manner as a result of cross-reaction.

Amino acids

Ádám Diós, Rita Elek, Ildikó Szabó, Szilvia Horváth, Judit Gyimesi, Róbert Király, Katharina Werkstetter, Sibylle Koletzko, László Fésüs, Ilma R Korponay-Szabó

Affiliations

  1. Department of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
  2. Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, Debrecen, Hungary.
  3. Coeliac Disease Center, Heim Pál National Pediatric Institute, Budapest, Hungary.
  4. Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
  5. Division of Gastroenterology and Hepatology, Department of Pediatrics, Dr. Von Hauner Children's Hospital, University Hospital, Ludwig-Maximilian's University Munich, Munich, Germany.
  6. Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland.
  7. Department of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. [email protected].
  8. Coeliac Disease Center, Heim Pál National Pediatric Institute, Budapest, Hungary. [email protected].

PMID: 34059947 PMCID: PMC8241804 DOI: 10.1007/s00726-021-03006-7

Abstract

Celiac disease (CeD) is a T-cell-dependent enteropathy with autoimmune features where tissue transglutaminase (TG2)-mediated posttranslational modification of gliadin peptides has a decisive role in the pathomechanism. The humoral immune response is reported to target mainly TG2-deamidated γ-gliadin peptides. However, α-gliadin peptides, like p57-68, playing a crucial role in the T-cell response, and p31-43, a major trigger of innate responses, also contain B-cell gliadin epitopes and γ-gliadin like motifs. We aimed to identify if there are anti-gliadin-specific antibodies in CeD patients targeting the p31-43 and p57-68 peptides and to examine whether deamidation of these peptides could increase their antigenicity. We explored TG2-mediated deamidation of the p31-43 and p57-68 peptides, and investigated serum antibody reactivity toward the native and deamidated α and γ-gliadin peptides in children with confirmed CeD and in prospectively followed infants at increased risk for developing CeD. We affinity-purified antibody populations utilizing different single peptide gliadin antigens and tested their binding preferences for cross-reactivity in real-time interaction assays based on bio-layer interferometry. Our results demonstrate that there is serum reactivity toward p31-43 and p57-68 peptides, which is due to cross-reactive γ-gliadin specific antibodies. These γ-gliadin specific antibodies represent the first appearing antibody population in infancy and they dominate the serum reactivity of CeD patients even later on and without preference for deamidation. However, for the homologous epitope sequences in α-gliadins shorter than the core QPEQPFP heptapeptide, deamidation facilitates antibody recognition. These findings reveal the presence of cross-reactive antibodies in CeD patients recognizing the disease-relevant α-gliadins.

Keywords: Antibody; Celiac disease; Cross-reactivity; Deamidation; Gliadin; Serum reactivity

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