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Peanut Sensitivity in Children Is Highlighted By Increased IL-13 Production and Cyp11a1 Expression
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Erwin W. Gelfand, MD FAAAAI, Meiqin Wang, MD, PhD, Carah B Santos, MD, Jennifer Fish, PNP, Bruce J. Lanser, MD
Rationale:

The pathobiology of peanut allergy is focused on IgE-mediated reactions. Genetic factors and critical pathways contribute to the risk of developing such reactions. The steroidogenic enzyme Cyp11a1 has been linked to development of allergic disease and IL-13 has been shown to play a role in IgE-mediated intestinal peanut allergy in mice. Activation of Cyp11a1 enzymatic activity was shown to be essential for IL-13 production and for development of peanut-induced intestinal anaphylaxis in mice.

Methods:

Human PBMCs from peanut-allergic children and healthy controls were isolated and stimulated with anti-human CD3/anti-CD28 for 48 hours. Cell supernatants were collected and cytokines measured by ELISA. Cyp11a1 expression levels were monitored by real-time PCR and protein expression in cells was detected by immunohistochemistry.  Peanut allergy was confirmed in all patients with a clinical history of reaction and/or evidence of sensitization (positive skin prick test or specific IgE) by double-blind, placebo-controlled oral food challenges to peanut protein.

Results:

Following activation, PBMCs from patients with peanut sensitivity had significantly increased production of IL-13 compared to controls but IFNg levels were similar between groups. Cyp11a1 protein and mRNA levels were significantly increased in PBMCs from patients with peanut sensitivity compared to controls.

Conclusions:

Cyp11a1 mRNA and protein expression and levels of IL-13 from activated T cells were significantly increased in peanut-allergic subjects, implicating this pathway in peanut-induced disease. Targeting this pathway may be an effective alternative or adjunct  to oral immunotherapy in the future.

Supported by Siemens, MW  by  Crawford Charitable Lead Unitrust, CS  by fellowship from Monsanto.