title: The copolymer P(HEMA-co-SS) binds gluten and reduces immune response in gluten-sensitized mice and human tissues.
abstract: OBJECTIVE
  Copolymers of hydroxyethyl methacrylate and styrene sulfonate complex with isolated gliadin (the toxic fraction of gluten) and prevent damage to the intestinal barrier in HLA-HCD4/DQ8 mice. We studied the activity toward gluten and hordein digestion and biologic effects of poly(hydroxyethyl methacrylate-co-styrene sulfonate (P(HEMA-co-SS)). We also investigated the effect of gliadin complex formation in intestinal biopsy specimens from patients with celiac disease.
  
  
  METHODS
  We studied the ability of P(HEMA-co-SS) to reduce digestion of wheat gluten and barley hordein into immunotoxic peptides using liquid chromatography-mass spectrometry. The biodistribution and pharmacokinetic profile of orally administered P(HEMA-co-SS) was established in rodents using tritium-labeled polymer. We assessed the capacity of P(HEMA-co-SS) to prevent the immunologic and intestinal effects induced by a gluten-food mixture in gluten-sensitized HLA-HCD4/DQ8 mice after short-term and long-term administration. We measured the effects of gliadin complex formation on cytokine release ex vivo using intestinal biopsy specimens from patients with celiac disease.
  
  
  RESULTS
  P(HEMA-co-SS) reduced digestion of wheat gluten and barley hordein in vitro, thereby decreasing formation of toxic peptides associated with celiac disease. After oral administration to rodents, P(HEMA-co-SS) was predominantly excreted in feces, even in the presence of low-grade mucosal inflammation and increased intestinal permeability. In gluten-sensitized mice, P(HEMA-co-SS) reduced paracellular permeability, normalized anti-gliadin immunoglobulin A in intestinal washes, and modulated the systemic immune response to gluten in a food mixture. Furthermore, incubation of P(HEMA-co-SS) with mucosal biopsy specimens from patients with celiac disease showed that secretion of tumor necrosis factor-α was reduced in the presence of partially digested gliadin.
  
  
  CONCLUSIONS
  The copolymer P(HEMA-co-SS) reduced digestion of wheat gluten and barley hordein and attenuated the immune response to gluten in a food mixture in rodents. It might be developed to prevent or reduce gluten-induced disorders in humans.
authors.affiliation: Faculty of Pharmacy, Université de Montréal, Montréal, Quebec, Canada.
authors.forename: Maud
authors.initials: M
authors.lastname: Pinier
authors.forename: Gregor
authors.initials: G
authors.lastname: Fuhrmann
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Galipeau
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rivard
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Murray
authors.forename: Chella S
authors.initials: CS
authors.lastname: David
authors.forename: Hana
authors.initials: H
authors.lastname: Drasarova
authors.forename: Ludmila
authors.initials: L
authors.lastname: Tuckova
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Leroux
authors.forename: Elena F
authors.initials: EF
authors.lastname: Verdu
mesh_terms: D000818:Animals; D002446:Celiac Disease / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D002853:Chromatography, Liquid; D004063:Digestion / Q000187:drug effects*; D005260:Female; D005903:Gliadin / Q000378:metabolism / Q000633:toxicity; D005983:Glutens / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D007583:Jejunum / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D010539:Permeability / Q000187:drug effects; D011102:Polyhydroxyethyl Methacrylate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D011137:Polystyrenes / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D011485:Protein Binding; D011897:Random Allocation; D051381:Rats; D013343:Styrenes / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D011137:Polystyrenes; D013343:Styrenes; C571891:poly(hydroxyethyl methacrylate-co-styrene sulfonate); D011102:Polyhydroxyethyl Methacrylate; D005983:Glutens; D005903:Gliadin