Salivary proline-rich proteins and gluten: Do structural similarities suggest a role in celiac disease?
OBJECTIVE
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.


METHODS
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
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.
Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA, USA.
Na
N
Tian
Dipartimento di Scienze della Vita e dell' Ambiente, Università di Cagliari, Cagliari, Italy.
Irene
I
Messana
Celiac Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Daniel A
DA
Leffler
Celiac Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Ciaran P
CP
Kelly
Celiac Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Joshua
J
Hansen
Dipartimento di Scienze della Vita e dell' Ambiente, Università di Cagliari, Cagliari, Italy.
Tiziana
T
Cabras
Dipartimento di Scienze della Vita e dell' Ambiente, Università di Cagliari, Cagliari, Italy.
Alfredo
A
D'Alessandro
Celiac Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|Institute of Translational Immunology and Research Center for Immunotherapy (FZI), University Medical Center, Mainz, Germany.
Detlef
D
Schuppan
Istituto di Biochimica e di Biochimica Clinica and/or Istituto per la Chimica del Riconoscimento Molecolare (CNR), Università Cattolica, Roma, Italy.
Massimo
M
Castagnola
Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA, USA.
Eva J
EJ
Helmerhorst
D000595:Amino Acid Sequence; D002446:Celiac Disease / Q000378:metabolism*; D005983:Glutens / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D055273:Salivary Proline-Rich Proteins / Q000737:chemistry*; D012471:Salivary Proteins and Peptides / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
D020033:Protein Isoforms; D055273:Salivary Proline-Rich Proteins; D012471:Salivary Proteins and Peptides; D005983:Glutens
Celiac disease; Gliadin; Proline-rich protein; Saliva