Methods: Fourteen subjects (median age 9 years) with allergy to walnut and another test tree nut (pecan, cashew, hazelnut, pistachio) were randomized (2:1) to receive WOIT or placebo OIT. Baseline and 38 week placebo-controlled OFCs were performed to walnut and a test tree nut. Skin prick testing (SPT), tree nut specific IgE, IgG4, basophil activation and cytokine production were analyzed. Outcomes were compared using Wilcoxon rank sum and Fisher’s exact tests.
Results: Subjects receiving WOIT (n=8) demonstrated significant increases in successfully consumed dose (SCD) compared with placebo OIT (median 5 g vs. 1 g; p=0.01). A significant increase in SCD was also observed during OFC to test tree nut in WOIT vs. placebo OIT subjects (median 3.75 vs. 0.25 g, p=0.001). All subjects receiving WOIT demonstrated significant increases in SCD from baseline to 38 week OFC for walnut (median 0.3 g baseline, 5 g 38 weeks) and test tree nut (0.3 g baseline, 3.75 g 38 weeks.) No severe symptoms were observed during the 38 week desensitization OFC. WOIT resulted in significant increases in walnut IgG4 (p=0.002); test tree nut IgG4 was also increased (p=0.09). Walnut- and tree nut specific IL-10 induction were observed with WOIT (p=0.06).
Conclusions: WOIT induces clinical desensitization to both walnut and a test tree nut after 38 weeks on therapy. Mechanistic changes supporting the development of sustained unresponsiveness were observed.