Na Tian1, Irene Messana2, Daniel A Leffler3, Ciaran P Kelly3, Joshua Hansen3, Tiziana Cabras2, Alfredo D'Alessandro2, Detlef Schuppan3,4, Massimo Castagnola5, Eva J Helmerhorst1. 1. Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA, USA. 2. Dipartimento di Scienze della Vita e dell' Ambiente, Università di Cagliari, Cagliari, Italy. 3. Celiac Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. 4. Institute of Translational Immunology and Research Center for Immunotherapy (FZI), University Medical Center, Mainz, Germany. 5. Istituto di Biochimica e di Biochimica Clinica and/or Istituto per la Chimica del Riconoscimento Molecolare (CNR), Università Cattolica, Roma, Italy.
Abstract
PURPOSE: Gluten proteins, the culprits in celiac disease (CD), show striking similarities in primary structure with human salivary proline-rich proteins (PRPs). Both are enriched in proline and glutamine residues that often occur consecutively in their sequences. We investigated potential differences in the spectrum of salivary PRPs in health and CD. EXPERIMENTAL DESIGN: Stimulated salivary secretions were collected from CD patients, patients with refractory CD, patients with gastrointestinal complaints but no CD, and healthy controls. PRP isoforms/peptides were characterized by anionic and SDS-PAGE, PCR, and LC-ESI-MS. RESULTS: The gene frequencies of the acidic PRP isoforms PIF, Db, Pa, PRP1, and PRP2 did not differ between groups. At the protein level, PRPs peptides showed minor group differences, but these could not differentiate the CD and/or refractory CDs groups from the controls. CONCLUSIONS AND CLINICAL RELEVANCE: This extensive study established that salivary PRPs, despite similarity to gluten proteins, show no apparent correlation with CD and thus will not serve as diagnostic markers for the disease. The structural basis for the tolerance to the gluten-like PRP proteins in CD is worthy of further exploration and may lead to the development of gluten-like analogs lacking immunogenicity that could be used therapeutically.
PURPOSE: Gluten proteins, the culprits in celiac disease (CD), show striking similarities in primary structure with human salivary proline-rich proteins (PRPs). Both are enriched in proline and glutamine residues that often occur consecutively in their sequences. We investigated potential differences in the spectrum of salivary PRPs in health and CD. EXPERIMENTAL DESIGN: Stimulated salivary secretions were collected from CD patients, patients with refractory CD, patients with gastrointestinal complaints but no CD, and healthy controls. PRP isoforms/peptides were characterized by anionic and SDS-PAGE, PCR, and LC-ESI-MS. RESULTS: The gene frequencies of the acidic PRP isoforms PIF, Db, Pa, PRP1, and PRP2 did not differ between groups. At the protein level, PRPs peptides showed minor group differences, but these could not differentiate the CD and/or refractory CDs groups from the controls. CONCLUSIONS AND CLINICAL RELEVANCE: This extensive study established that salivary PRPs, despite similarity to gluten proteins, show no apparent correlation with CD and thus will not serve as diagnostic markers for the disease. The structural basis for the tolerance to the gluten-like PRP proteins in CD is worthy of further exploration and may lead to the development of gluten-like analogs lacking immunogenicity that could be used therapeutically.
Authors: L Willemijn Vader; Arnoud de Ru; Yvonne van der Wal; Yvonne M C Kooy; Willemien Benckhuijsen; M Luisa Mearin; Jan Wouter Drijfhout; Peter van Veelen; Frits Koning Journal: J Exp Med Date: 2002-03-04 Impact factor: 14.307
Authors: Na Tian; Lina Faller; Daniel A Leffler; Ciaran P Kelly; Joshua Hansen; Jos A Bosch; Guoxian Wei; Bruce J Paster; Detlef Schuppan; Eva J Helmerhorst Journal: Appl Environ Microbiol Date: 2017-03-02 Impact factor: 4.792
Authors: Na Tian; Daniel A Leffler; Ciaran P Kelly; Joshua Hansen; Eric V Marietta; Joseph A Murray; Detlef Schuppan; Eva J Helmerhorst Journal: Am J Physiol Gastrointest Liver Physiol Date: 2015-10-01 Impact factor: 4.052