The Copolymer P(HEMA-co-SS) Binds Gluten and Reduces Immune Response in Gluten-Sensitized Mice and Human Tissues

Published:November 11, 2011DOI:

      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.


      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.


      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.


      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.


      Abbreviations used in this paper:

      BSA (bovine serum albumin), GFD (gluten-free diet), HD (high dose), IL (interleukin), LC-MS (liquid chromatography–mass spectrometry), LD (low dose), MCP-1 (monocyte chemotactic protein 1), P(HEMA-co-SS) (poly(hydroxyethyl methacrylate-co-styrene sulfonate)), PT (peptic-tryptic), TNF (tumor necrosis factor)
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