Published Online: December 24, 2014
Several recent clinical trials have demonstrated that oral (OIT) and sublingual (SLIT) immunotherapy for peanut and other food allergies can effectively increase the amount of the problematic food patients are able to eat before they experience an allergic reaction. Unfortunately, only a minority of patients (about 20-30%) maintain this unresponsiveness long-term, suggesting that most patients fail to achieve “true tolerance” to the food. In a recent article published in The Journal of Allergy and Clinical Immunology (JACI), Gorelik and colleagues asked how these therapies affected patients’ immune responses to the food allergen, and how these cellular changes relate to the patients’ reaction to the food both during treatment and after discontinuing the therapy.
The authors performed their study as part of a clinical trial seeking to compare the effectiveness of SLIT versus the effectiveness of OIT in patients with peanut allergy (see accompanying article by Narisety et al. in the same journal issue). Their study focuses on three main cell types in the blood: 1) basophils, cells which can respond immediately upon exposure to allergen by releasing chemical mediators such as histamine that are responsible for producing symptoms of an acute allergic reaction; 2) dendritic cells (DCs), which process allergen and present it to the immune system; and 3) T cells, which drive either an allergic response, or a response of tolerance to food allergens, depending upon signals derived from DCs.
As expected, before beginning treatment, all cellular studies reflected the patients’ severe allergic reactivity to peanut. During the “build-up” phase of the study, as subjects’ were given larger and larger doses of peanut, there was evidence that allergic responses lessened. In general, subjects whose basophils exhibited less reaction to peanut at baseline responded most favorably to immunotherapy. Interestingly, suppression in cellular reactivity was not only seen in response to peanut but also dust mite, an unrelated allergen for which subjects had not received treatment. However, four weeks after the treatment had ended, and in some cases while they continued to ingest peanut in their diet, cells from many subjects regained allergic activities and behaved nearly as they had at baseline.
The results of this study suggest that SLIT and OIT for peanut may effectively suppress the activities of multiple cell types critical in generating allergic immune responses, but frequently this decrease in allergic responses did not persist, particularly once subjects discontinued treatment and in some cases while they remained on therapy. Although there was a great deal of inter-individual variation and often cellular outcomes did not correlate well with clinical outcomes, Gorelik et al.’s findings may provide a hint as to why current SLIT and OIT protocols for food allergy have not produced sustained clinical tolerance in most patients.
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.