The copolymer P(HEMA-co-SS) binds gluten and reduces immune response in gluten-sensitized mice and human tissues

Pinier M, Fuhrmann G, Galipeau HJ, Rivard N, Murray JA, David CS, Drasarova H, Tuckova L, Leroux JC, Verdu EF (2012)

Publication Type: Journal article

Publication year: 2012

Journal

Gastroenterology Elsevier

Book Volume: 142

Pages Range: 316-325.e12

Journal Issue: 2

DOI: 10.1053/j.gastro.2011.10.038

Abstract

Background & Aims: 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 chromatographymass 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. © 2012 AGA Institute.

Authors with CRIS profile

Gregor Fuhrmann

Involved external institutions

Université de Montréal CA Canada (CA) Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich CH Switzerland (CH) McMaster University CA Canada (CA) Université de Sherbrooke CA Canada (CA) Mayo Clinic US United States (USA) (US) Academy of Sciences of the Czech Republic (ASCR) / Akademie věd České republiky (AVČR) CZ Czech Republic (CZ)

How to cite

APA:

Pinier, M., Fuhrmann, G., Galipeau, H.J., Rivard, N., Murray, J.A., David, C.S.,... Verdu, E.F. (2012). The copolymer P(HEMA-co-SS) binds gluten and reduces immune response in gluten-sensitized mice and human tissues. Gastroenterology, 142(2), 316-325.e12. https://dx.doi.org/10.1053/j.gastro.2011.10.038

MLA:

Pinier, Maud, et al. "The copolymer P(HEMA-co-SS) binds gluten and reduces immune response in gluten-sensitized mice and human tissues." Gastroenterology 142.2 (2012): 316-325.e12.

BibTeX: Download