Vanitha Sampath

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.

New treatment directions in food allergy

There is general consensus that food allergies (FAs) are increasing in prevalence. However, because of the lack of a simple diagnostic test for food allergy and methodological differences between studies to determine prevalence of food allergy, true food allergy prevalence in the past or present is difficult to determine.1 On the basis of a number of studies, FA is now estimated to affect about 5% of adults and 8% of children.2 Increases in the rate of emergency department visits and hospital admissions due to food-induced anaphylaxis among children have been reported.3 These increases in rates of FA are worrisome and have intensified research into effective treatments for the disease. At the present time, there is no FDA-approved treatment for FA and the standard of care is individualized avoidance of the offending food allergens and treatment of symptoms on accidental ingestion.2 Allergen avoidance is difficult to accomplish as many allergenic foods, such as milk, eggs, and peanuts are common ingredients in many foods. Accidental ingestion is common and one study reported that during a 5- and 10-year follow-up period, 58% and 75% individuals with peanut allergy, respectively, accidentally consume peanuts.4 Constant vigilance and monitoring of foods for potential allergens leads to stress and lowers quality of life. Localized reactions on accidental ingestion are treated with antihistamines or glucocorticoids while systemic reactions are treated with epinephrine.5 These pharmaceutical agents, however, are inadequate and offer only symptomatic relief and do not address the underlying immune disorder. Food allergies are classified into IgE-mediated, non-IgE-mediated, and mixed (non-IgE and IgE-mediated). Although this classification is an oversimplification of the various pathologies underlying food allergies, it plays an essential part in diagnosis and treatment. IgE-mediated reactions are immediate (minutes to within 1–2 hours) and symptoms include urticaria, nausea, abdominal pain, respiratory symptoms, and potentially fatal systemic anaphylaxis. Non-IgE-mediated reactions are delayed and include food protein-induced allergic enterocolitis, food protein-induced allergic proctocolitis, and food protein-induced enteropathy. Eosinophilic gastrointestinal disorders constitute another group of FA disorders with chronic eosinophilic infiltration of the gastrointestinal wall.6 These were initially considered to be mixed (both IgE and non-IgE-mediated) but currently the role of IgE in these diseases is controversial.6–8 This review focuses on current treatments that show promise in desensitizing individuals with IgE-mediated FA.

Combining anti-IgE with oral immunotherapy

Food allergy is a significant medical problem that affects up to 8% of children in developed countries. At present, there are no curative therapies available in routine practice and management of food allergy involves strict allergen avoidance, education, and prompt treatment upon accidental exposure. Oral immunotherapy (OIT) is an efficacious experimental approach to food allergy and has been shown to provide a substantial benefit in terms of allergen desensitization. However, OIT is associated with high rates of allergic reactions, and the period of protection offered by OIT appears to be limited and highly variable. Recurrence of allergen sensitivity after a period of treatment discontinuation is commonly observed. With the aim of overcoming these limitations of OIT, several trials have studied omalizumab (anti‐IgE monoclonal antibody) as an adjuvant treatment for patients undergoing OIT. Results from these trials have shown that the addition of omalizumab to OIT leads to a significant decrease in the frequency and severity of reactions, which allows for an increase in the threshold of tolerance to food allergens. This review provides a summary of the current literature and addresses some of the key questions that remain regarding the use of omalizumab in conjunction with OIT.

Deciphering the black box of food allergy mechanisms.

OBJECTIVE To review our current understanding of immunotherapy, the immune mechanisms underlying food allergy, and the methodological advances that are furthering our understanding of the role of immune cells and other molecules in mediating food allergies. DATA SOURCES Literature searches were performed using the following combination of terms: allergy, immunotherapy, food, and mechanisms. Data from randomized clinical studies using state-of-the-art mechanistic tools were prioritized. STUDY SELECTIONS Articles were selected based on their relevance to food allergy. RESULTS Current standard of care for food allergies is avoidance of allergenic foods and the use of epinephrine in case of severe reaction during unintentional ingestion. During the last few decades, great strides have been made in understanding the cellular and molecular mechanisms underlying food allergy, and this information is spearheading the development of exciting new treatments. CONCLUSION Immunotherapy protocols are effective in desensitizing individuals to specific allergens; however, recurrence of allergic sensitization is common after discontinuation of therapy. Interestingly, in a subset of individuals, immunotherapy is protective against allergens even after discontinuation of immunotherapy. Whether this protection is permanent is currently unknown because of inadequate long-term follow-up data. Research on understanding the underlying mechanisms may assist in modifying protocols to improve outcome and enable sustained unresponsiveness, rather than a temporary relief against food allergies. The cellular changes brought about by immunotherapy are still a black box, but major strides in our understanding are being made at an exciting pace.

Food allergy and omics

Food allergy (FA) prevalence has been increasing over the last few decades and is now a global health concern. Current diagnostic methods for FA result in a high number of false-positive results, and the standard of care is either allergen avoidance or use of epinephrine on accidental exposure, although currently with no other approved treatments. The increasing prevalence of FA, lack of robust biomarkers, and inadequate treatments warrants further research into the mechanism underlying food allergies. Recent technological advances have made it possible to move beyond traditional biological techniques to more sophisticated high-throughput approaches. These technologies have created the burgeoning field of omics sciences, which permit a more systematic investigation of biological problems. Omics sciences, such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiomics, and exposomics, have enabled the construction of regulatory networks and biological pathway models. Parallel advances in bioinformatics and computational techniques have enabled the integration, analysis, and interpretation of these exponentially growing data sets and opens the possibility of personalized or precision medicine for FA.

The Use of Biomarkers to Predict Aero-Allergen and Food Immunotherapy Responses

The incidence of allergic conditions has continued to rise over the past several decades, with a growing body of research dedicated toward the treatment of such conditions. By driving a complex range of changes in the underlying immune response, immunotherapy is the only therapy that modulates the immune system with long-term effects and is presently utilized for the treatment of several atopic conditions. Recent efforts have focused on identifying biomarkers associated with these changes that may be of use in predicting patients with the highest likelihood of positive clinical outcomes during allergen immunotherapy (AIT), providing guidance regarding AIT discontinuation, and predicting symptomatic relapse and the need for booster AIT after therapy. The identification of such biomarkers in food allergy has the additional benefit of replacing oral food challenges, which are presently the gold standard for diagnosing food allergies. While several markers have shown early promise, research has yet to identify a marker that can invariably predict clinical response to AIT. Skin prick testing (SPT) and specific IgE have commonly been used as inclusion criteria for the initiation of AIT and prediction of reactions during subsequent allergen challenge; however, existing data suggests that changes in these markers are not always associated with clinical improvement and can be widely variable, reducing their utility in predicting clinical response. Similar findings have been described for the use of allergen-specific functional IgG4 antibodies, basophil activation and histamine release, and type 2 innate lymphoid cells. There appears to be a promising association between changes in the expression of dendritic cell-associated markers, as well as the use of DNA promoter region methylation patterns in the prediction of allergy status following therapy. The cellular and molecular changes brought about by immunotherapy are still under investigation, but major strides in our understanding are being made.

Cord blood T cell subpopulations and associations with maternal cadmium and arsenic exposures

Background Arsenic and cadmium are environmental pollutants, and although the evidence for adverse immune effects after prenatal arsenic and cadmium exposures is increasing, little is known about the underlying immunological mechanisms. Methods We investigated the relationship between prenatal arsenic and cadmium exposures and a variety of T cell subpopulations measured in cord blood for 63 participants in the New Hampshire Birth Cohort Study. Post-partum toenail concentrations of arsenic and cadmium were used as an estimate of maternal exposure during pregnancy. The characteristics of cord blood proportions of T lymphocytes and subpopulations (expression of markers for Th1, Th2, Th17, Th1Th17, induced and natural regulatory T cells and NKTs) are presented. Results In regression analyses, maternal arsenic exposure levels were inversely associated with cord blood T helper memory cells (-21%, 95% CI: -36%, -3%) and the association was found to be stronger in females. They were also inversely associated with activated T helper memory cells, particularly in males (-26%, 95% CI: -43%, -3%). Similarly, inverse associations were observed between cadmium exposure levels and activated T helper memory cells (-16%, 95% CI: -30%, -1%) and also for T helper memory cells in females (-20%, 95% CI: -35%, -3%). Conclusion The results suggest that prenatal exposures to relatively low levels of arsenic and cadmium may contribute to altered distribution of T cell populations at birth. These changes in theory, could have contributed to the previously reported immunosuppressive effects observed later in infancy/childhood.

Impact of allergen immunotherapy in allergic asthma

Although traditional pharmacological approaches improve outcomes in disease management for allergic asthma, these fail to modify the underlying immune responses. Allergen immunotherapy remains the only etiological therapy for the treatment of respiratory allergies for which clinical efficacy has been demonstrated through several well-controlled studies. In this review, we examine evidence from the past 5 years regarding the impact of allergen immunotherapy on allergic asthma to inform practitioners and stimulate further discussion and research.