Whitney Block

Anti-IgE treatment with oral immunotherapy in multifood allergic participants: a double-blind, randomised, controlled trial

Summary BACKGROUND Despite progress in single food oral immunotherapy (OIT), there is little evidence concerning the safety and efficacy of treating individuals with multiple food (multifood) allergies. We conducted a pilot study testing whether anti-IgE (omalizumab) combined with multifood OIT benefitted multifood allergic patients. METHODS In this blinded, phase 2 clinical trial conducted at Stanford University, 48 participants, aged 4-15 years, with multifood allergies validated by double-blind, placebo-controlled food challenges (DBPCFCs) to their offending foods were block randomized (3:1) to receive multifood OIT to 2-5 foods, together with omalizumab (n=36) or placebo (n=12). Omalizumab or placebo was administered subcutaneously for 16 weeks with OIT starting at week 8; omalizumab or placebo was stopped 20 weeks before exit DBPCFCs (week 36) to determine the primary endpoint: the proportion of participants who passed DBPCFCs to at least 2 of their offending foods. This completed trial is registered with ClinicalTrials.gov, . FINDINGS At week 36, a significantly greater proportion of the omalizumab (30/36, 83%) vs. placebo (4/12, 33%) participants passed DBPCFCs to 2 g protein for ≥ 2 of their offending foods (odds ratio (OR): 10, 95% confidence interval (CI): 1·8, 58·3, P=0·004). The same individuals also tolerated 4 g protein of ≥ 2 foods (secondary endpoint, P=0·004). A greater proportion of omalizumab (13/17, 77%) vs. placebo (0/5, 0%) participants passed a DBPCFC to 2 g protein for ≥ 4 of their offending foods (OR: 33, 95% CI: 1·9, ∞, P=0·01). All participants completed the study. There were no serious or severe (≥ grade 3) adverse events. INTERPRETATION In multifood allergic patients, omalizumab improves the efficacy of multifood OIT and enables safe and rapid desensitization. FUNDING NIH U19 AADCRC and Opportunity Fund, Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Simons Foundation, Myra Reinhard Foundation, FARE Center of Excellence, Department of Pathology, and Department of Pediatrics, Stanford University.

Association of Clinical Reactivity with Sensitization to Allergen Components in Multifood-Allergic Children

BACKGROUND Thirty percent of children with food allergies have multiple simultaneous allergies; however, the features of these multiple allergies are not well characterized serologically or clinically. OBJECTIVE We comprehensively evaluated 60 multifood-allergic patients by measuring serum IgE to key allergen components, evaluating clinical histories and medication use, performing skin tests, and conducting double-blind, placebo-controlled food challenges (DBPCFCs). METHODS Sixty participants with multiple food allergies were characterized by clinical history, DBPCFCs, total IgE, specific IgE, and component-resolved diagnostics (IgE and IgG4) data. The food allergens tested were almond, egg, milk, sesame, peanut, pecan, walnut, hazelnut, cashew, pistachio, soy, and wheat. RESULTS Our data demonstrate that of the reactions observed during a graded DBPCFC, gastrointestinal reactions occurred more often in boys than in girls, as well as in individuals with high levels of IgE to 2S albumins from cashew, walnut, and hazelnut. Certain food allergies often occurred concomitantly in individuals (ie, cashew/pistachio and walnut/pecan/hazelnut). IgE testing to components further corroborated serological relationships between and among these clustered food allergies. CONCLUSIONS Associations of certain food allergies were shown by DBPCFC outcomes as well as by correlations in IgE reactivity to structurally related food allergen components. Each of these criteria independently demonstrated a significant association between allergies to cashew and pistachio, as well as among allergies to walnut, pecan, and hazelnut.

Peanut-specific type 1 regulatory T cells induced in vitro from allergic subjects are functionally impaired

&NA; Figure. No caption available. Background: Peanut allergy (PA) is a life‐threatening condition that lacks regulator‐approved treatment. Regulatory T type 1 (TR1) cells are potent suppressors of immune responses and can be induced in vivo upon repeated antigen exposure or in vitro by using tolerogenic dendritic cells. Whether oral immunotherapy (OIT) leads to antigen‐specific TR1 cell induction has not been established. Objectives: We sought to determine whether peanut‐specific TR1 cells can be generated in vitro from peripheral blood of patients with PA at baseline or during OIT and whether they are functional compared with peanut‐specific TR1 cells induced from healthy control (HC) subjects. Methods: Tolerogenic dendritic cells were differentiated in the presence of IL‐10 from PBMCs of patients with PA and HC subjects pulsed with the main peanut allergens of Arachis hypogaea, Ara h 1 and 2, and used as antigen‐presenting cells for autologous CD4+ T cells (CD4+ T cells coincubated with tolerogenic dendritic cells pulsed with the main peanut allergens [pea‐T10 cells]). Pea‐T10 cells were characterized by the presence of CD49b+ lymphocyte‐activation gene 3 (LAG3)+ TR1 cells, antigen‐specific proliferative responses, and cytokine production. Results: CD49b+LAG3+ TR1 cells were induced in pea‐T10 cells at comparable percentages from HC subjects and patients with PA. Despite their antigen specificity, pea‐T10 cells of patients with PA with or without OIT, as compared with those of HC subjects, were not anergic and had high TH2 cytokine production upon peanut‐specific restimulation. Conclusions: Peanut‐specific TR1 cells can be induced from HC subjects and patients with PA, but those from patients with PA are functionally defective independent of OIT. The unfavorable TR1/TH2 ratio is discussed as a possible cause of PA TR1 cell impairment.

Diagnosis of Food Allergy

The prevalence of food allergies has been on the increase over the last 2 decades. Diagnosing food allergies can be complicated, as there are multiple types that have distinct clinical and immunologic features. Food allergies are broadly classified into immunoglobulin E (IgE)-mediated, non-IgE-mediated, or mixed food allergic reactions. This review focuses on the clinical manifestations of the different categories of food allergies and the different tests available to guide the clinician toward an accurate diagnosis.

Elimination diet and the development of multiple tree-nut allergies

BackgroundDespite its high prevalence, relatively little is known about the characteristics of patients with multiple tree-nut allergies.MethodsPatients (n=60, aged 4–15 years), recruited for a multiple food (tree nuts, peanut, milk, egg, soy, sesame, and wheat) oral immunotherapy (OIT) study, filled a questionnaire on their initial allergy evaluation. Medical records were reviewed. At OIT enrollment (median interval, 7.5 years), patients underwent oral food challenges (OFCs) to foods still eliminated.ResultsThere was significantly less evidence for eliminating tree nuts compared with other foods, as reflected by a lower rate of acute reaction to the offending food, either as the trigger for initial allergy evaluation (5.9% for tree-nuts vs. 20–40% for other foods, respectively P<0.001) or later in life (14.5% vs. 38–75%, respectively P=0.001), and a higher rate of negative skin prick test (SPT)/specific IgE (sIgE) at initial diagnosis (25% vs. <10%, P<0.001). SPT/sIgE increased significantly from past initial levels to present for tree nuts (P<0.001) and peanut (P=0.001) but not for other foods, and most OFCs performed at present were positive.ConclusionsTree nuts are often eliminated from the diet of multiple-food-allergic patients, despite their low probability for allergy. Sensitization and allergy to most tree nuts exist years later, suggesting that it developed during the period of elimination.