Clinical Immunology & Research

Abstract

Systemic TNF-α Reduction by Blocking IgE-mediated Cellular Activation in Inflammatory Bowel Disease

Rachael E. Hamilton BA, Singh Vikram M.D, Francis A. Farraye, M.D., MSc, John H. Connor Ph.D, Lisa M. Ganley-Leal, Ph.D.

Background: Several cells bearing IgE receptors and IgE circulate in the bloodstream, including basophils. The roles of IgE and IgE-bearing cells have not been well-characterized in inflammatory bowel disease (IBD). Recently, investigators reported that basophils are elevated and may promote inflammatory T cells in IBD. Basophils secrete TNF-α in response to IgE cross-linking suggesting a role in mediating inflammation. We sought to determine the effects of ET523, a drug that reduces IgE-mediated cellular activation, on basophil function and TNF-α secretion in IBD. Anti-IgE cross-linking induced basophil activation and cytokine secretion from cells from Crohn’s disease and ulcerative colitis patients. Cells treated with ET523 reduced anti-IgE mediated cellular activation and TNF-α secretion. Importantly, ET523 reduced unstimulated, basal secretion of TNF-α in IBD. IgE-mediated cellular activation may play a role in systemic TNF-α production in IBD. ET523 appears effective at reducing TNF-α secretion and thus represents a novel agent to treat IBD.

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