Oral tolerance in patients with food protein induced enterocolitis syndrome (FPIES); Evidence of impaired induction of oral tolerance in FPIES patients with persistent reaction to multiple foods (123.9)

Abstract

Abstract Treatment for FPIES is the avoidance of offending food, i.e., a restricted diet (RD). While most FPIES children are good responders to the RD (FPIES-GR), some are not (FPIES-poor responders: FPIES-PR) with persistent non-IgE mediated reactivity to multiple foods. This study assessed production of counter-regulatory cytokines crucial for oral tolerance by peripheral blood mononuclear cells (PBMCs) in FPIES-PR (N=18, 0.6 -4.8 yr), FPIES-GR (N=22, 1.1-5.9 yr), and normal control (N=19, 1.0-5.7 yr) children after FPIES children were on the RD. PBMCs were stimulated with agonists of toll like receptors (TLRs) and representative luminal antigens (Ags) (soy, cow’s milk, and wheat proteins, and candida Ag). Microarray analysis of PB moncytes was also performed on samples from some of these children. FPIES-PR children revealed more severe clinical features including failure to thrive, intolerance to probiotics, and anaphylaxis like reaction to rice than FPIES-GR children (p<0.005). FPIES-PR PBMCs produced less sTNFRII and IL-10 both with TLR agonists and without a stimulus than the control groups. FPIRS-PR cells also produced less IL-6 with a TLR4 agonist and without a stimulus than normal controls (p<0.05). Such changes were not observed in FPIES-GR cells. FPIES-PR PBMCs produced less TGF-β with and without luminal Ag than PFIES-GR PBMCs. Taken together, FPIES-PR children may have impaired production of counter-regulatory cytokines that are crucial for oral tolerance.