Clinical efficacy and immune regulation with peanut oral immunotherapy

Abstract

Background: Oral immunotherapy (OIT) has been thought to induce clinical desensitization to allergenic foods, but trials coupling the clinical response and immunologic effects of peanut OIT have not been reported.

Objective: The study objective was to investigate the clinical efficacy and immunologic changes associated with OIT.

Methods: Children with peanut allergy underwent an OIT protocol including initial day escalation, buildup, and maintenance phases, and then oral food challenge. Clinical response and immunologic changes were evaluated.

Results: Of 29 subjects who completed the protocol, 27 ingested 3.9 g peanut protein during food challenge. Most symptoms noted during OIT resolved spontaneously or with antihistamines. By 6 months, titrated skin prick tests and activation of basophils significantly declined. Peanut-specific IgE decreased by 12 to 18 months, whereas IgG(4) increased significantly. Serum factors inhibited IgE-peanut complex formation in an IgE-facilitated allergen binding assay. Secretion of IL-10, IL-5, IFN-gamma, and TNF-alpha from PBMCs increased over a period of 6 to 12 months. Peanut-specific forkhead box protein 3 T cells increased until 12 months and decreased thereafter. In addition, T-cell microarrays showed downregulation of genes in apoptotic pathways.

Conclusion: Oral immunotherapy induces clinical desensitization to peanut, with significant longer-term humoral and cellular changes. Microarray data suggest a novel role for apoptosis in OIT.

Figure 1. Effect of Peanut OIT on Basophil Activation

Top row: subjects who received peanut OIT. Bottom row: subjects in an observational study of peanut allergy. At a peanut concentration of 10 μg/mL, OIT results in significant initial changes in basophil responsiveness (*P < 0.001).

Figure 2. Serum Levels of Peanut-Specific Immunoglobulins During Peanut OIT

In the serum of 28 subjects undergoing immunotherapy, peanut-specific IgE (A), IgG (B), and IgG4 (C) were measured by using the ImmunoCAP instrument. Values are log-transformed, and median and mean values are represented by black and yellow horizontal lines, respectively. A mixed model, repeated measures ANOVA was used to determine the statistical significance between baseline and treatment time points (*P < 0.0005).

Figure 3. Peanut OIT Leads to FAB Inhibition

Blue lines represent individual data points; red line the mean. Statistical differences between pre-OIT and 12-month–post-OIT serum were determined by Wilcoxon signed rank test (*P < 0.001).

Figure 4. Cytokines Secreted From PBMCs After ConA Stimulation

The above 6 cytokines/chemokines had statistically significant changes versus medium alone (P < 0.05). Black lines are median values; red lines are means.

Figure 5. Cytokines Secreted From PBMCs Stimulated With Crude Peanut Extract

The above 6 cytokines/chemokines had statistically significant changes versus medium alone (P < 0.05). Black lines are median values; yellow lines are means.

Figure 6. Changes of FoxP3⁺ Regulatory T cells During Peanut Oral Immunotherapy

PBMCs from 10 subjects were cultured in presence of peanut proteins, Ara h 2, or medium alone (RPMI). Paired t-tests were employed to determine statistical differences between baseline and later time points (P < 0.05, 6 months; P < 0.01, 12 months).