Innate Immune Responses Differ In Patients With Food Protein Induced Enterocolitis Syndrome (fpies) Who Respond Well To The Restrictive Diet And Those Who Do Not

Abstract

FPIES is a benign condition with an excellent response to the avoidance of the offending food, i.e., restrictive diet (RD). This study hypothesized that FPIES patients with poor responses to the RD (FPIES-PR) have innate immune abnormalities compared to those with good responses to the RD (FPIES-GR). This study include FPIES-PR (N=18, 1.1 -5.1 yr), FPIES-GR (N=18, 0.6-4.8 yr), and normal control (N=16, 1.0-5.5 yr) children. In addition to detailed clinical features and routine food allergy (FA) workup, we examined responses to agonists of toll like receptors (TLRs) and representative luminal antigens (Ags) (soy, cow's milk, and wheat proteins, and candida Ag) by measuring production of proinflammatory and counter-regulatory cytokines by peripheral blood mononuclear cells (PBMCs) when their GI symptoms were under control following implementation of the RD. FPIES-PR children revealed more severe clinical features as evidenced by higher frequency of failure to thrive (FTT), requirement for the use of free amino acid (FAA) formulas, intolerance to probiotics, and severe anaphylaxis like reaction to rice than FPIES-GR children (all p<0.005). FPIES-PR PBMCs revealed lower production of counter-regulatory cytokine (sTNFRII and IL-10) in the absence of stimulus and with TLR 5, 7/8, and 9 agonists (sTNFRII) and with TLR2/6, 5, and 9 agonists (IL-10) as compared to normal controls. FPIES-GR PBMCs only revealed lower IL-10 production with TLR2/6 agonist than controls. These findings indicate that decreased production of counter-regulatory cytokines in response to stimuli of innate immunity may be associated with apparent failure of developing oral tolerance in FPIES-PR children.