Immunotherapy, rather than avoidance, modifies antibody responses in peanut allergy
Published Online: November 29, 2012
Several clinical trials have now demonstrated that most subjects receiving peanut oral immunotherapy (OIT) experience a reduction in allergy response, or clinical reactivity, a process referred to as desensitization. In parallel, OIT changes many aspects of the immune response to peanut. These processes are being intensely studied to understand the mechanisms responsible for OIT’s clinical effects.
In an article recently published in The Journal of Allergy and Clinical Immunology (JACI), Vickery et al analyzed serum antibody responses over several years in 28 individuals with persistent peanut allergy, of whom 22 were receiving peanut OIT and six were control subjects continuing to avoid peanut. To do this, the authors utilized a technology called a peptide microarray system, which identifies precisely where IgE and IgG4 antibodies bind to the major peanut allergens Ara h 1, 2, and 3. This technique enabled examination of the antibody repertoire with much higher resolution than the commercially available forms of IgE testing used in clinical practice.
In control subjects, the authors found broadly diverse and highly stable IgE and IgG4 antibody repertoires that did not substantially change after years of allergen avoidance diets, the standard of care approach. In contrast, subjects receiving OIT experienced extensive and complex changes in antibody quantity and binding patterns. In particular, the authors observed a significant reduction in the total amount of peanut-specific IgE in all OIT subjects, and in most subjects, the diversity of IgE binding to Ara h 1, 2, and 3 also decreased over time. Meanwhile IgG4 binding significantly increased over time. These changes occurred widely, including at informative “hotspots” within these major allergens that in previous microarray studies had been shown to associate with tolerance development.
This was the first study to examine in detail the antibody changes that occur during OIT, and one of the first microarray studies to analyze the same individuals multiple times over the course of several years. The findings suggest that whereas allergen avoidance diets do not alter binding patterns in patients with persistent peanut allergy, OIT can induce changes similar to those seen in previously published studies of individuals experiencing successful immunotherapy or development of natural tolerance to previously allergenic foods. The authors are currently performing additional studies to determine if the changes they observed in binding patterns are linked to successful outcomes after OIT.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.