Food allergy is increasing in school-age children. School nurses are a primary health care resource for children with food allergy and must be prepared to manage allergen avoidance and respond in the event of an allergic reaction. An anonymous survey was administered to school nurses attending their association meetings to determine their educational needs regarding children with food allergy. With 199 school nurses responding, their self-reported proficiency for critical areas of food allergy knowledge and management varied, with weaknesses identified particularly for emergency plan development, staff education, delegation, developing guidelines for banning foods and planning school trips. Nurses reported a high interest in obtaining educational materials in these areas and prefer video and Internet resources that could be promoted through professional organizations.
school nurses; food allergy; education; emergency plan
Peanut-allergic subjects have highly stable pathologic antibody repertoires to the immunodominant B cell epitopes of the major peanut allergens Ara h 1-3.
We used a peptide microarray technique to analyze the effect of treatment with peanut oral immunotherapy (OIT) on such repertoires.
Measurements of total peanut-specific IgE (psIgE) and psIgG4 were made with CAP-FEIA. We analyzed sera from 22 OIT subjects and 6 controls and measured serum specific IgE and IgG4 binding to epitopes of Ara h 1-3 using a high-throughput peptide microarray technique. Antibody affinity was measured using a competitive peptide microarray as previously described.
At baseline, psIgE and psIgG4 diversity were similar between subjects and controls, and there was broad variation in epitope recognition. After a median 41 months of OIT, polyclonal psIgG4 increased from a median 0.3 mcg/mL (IQR 0.1-0.43) at baseline to 10.5 mcg/mL (3.95-45.48) (p<0.0001) and included de novo specificities. PsIgE was reduced from a median baseline of 85.45 kUA/L (23.05-101.0) to 7.75 kUA/L (2.58-30.55) (p<0.0001). Affinity was unaffected. Although the psIgE repertoire contracted in most OIT-treated subjects, several subjects generated new IgE specificities even as the total psIgE decreased. Global epitope-specific shifts from IgE to IgG4 binding occurred, including at an informative epitope of Ara h 2.
OIT differentially alters Ara h 1-3 binding patterns. These changes are variable between subjects, not observed in controls, and include a progressive polyclonal increase in IgG4, with concurrent reduction in IgE amount and diversity.
peanut allergy; oral immunotherapy; IgE; IgG4; peptide microarray; epitope; B cell; antibody affinity
There are presently no available therapeutic options for peanut-allergic patients.
To investigate the safety, efficacy, and immunologic effects of peanut sublingual immunotherapy (SLIT).
After a baseline oral food challenge (OFC) of up to 2g of peanut powder (~50% protein) (median successfully consumed dose [SCD] 46mg), 40 subjects, aged 12–37 (median 15) years, were randomized 1:1 across 5 sites to daily peanut or placebo SLIT. A 5g OFC was performed after 44 weeks followed by unblinding; placebo subjects then crossed over to higher dose peanut SLIT, followed by a subsequent crossover Week 44 5g OFC. Week 44 OFCs from both groups were compared to baseline OFCs; subjects successfully consuming 5g or at least 10-fold more peanut powder than the baseline OFC threshold were considered responders.
After 44 weeks of SLIT, 14/20 (70%) subjects receiving peanut SLIT were responders compared to 3/20 (15%) subjects receiving placebo (p<0.001). In peanut-SLIT responders, median SCD increased from 3.5mg to 496mg. After 68 weeks of SLIT, median SCD significantly increased to 996mg (compared to week 44, p=0.05). The median SCD at the Week 44 crossover OFC was significantly higher than baseline (603mg vs 71mg; p=0.02). 7/16 (44%) crossover subjects were responders; median SCD increased from 21mg to 496mg among responders. Of 10,855 peanut doses through Week 44 OFCs, 63.1% were symptom-free; excluding oral/pharyngeal symptoms, 95.2% were symptom-free.
Peanut SLIT safely induced a modest level of desensitization in a majority of subjects compared to placebo. Longer duration of therapy showed statistically significant increases in the SCD.
peanut allergy; sublingual immunotherapy; desensitization; food allergy
IgE-mediated allergic reactions to cashews and other nuts can trigger life-threatening anaphylaxis. Proactive therapies to decrease reaction severity do not exist.
We aimed to determine the efficacy of pepsin-digested cashew proteins used as immunotherapy in a murine model of cashew allergy.
Mice were sensitized to cashew and then underwent challenges with digested or native cashew allergens to assess the allergenicity of the protein preparations. Using native or pepsinized cashew proteins, mice underwent oral or intraperitoneal sensitization protocols to determine the immunogenic properties of the protein preparations. Finally, cashew-sensitized mice underwent an immunotherapy protocol with native or pepsinized cashew proteins and subsequent provocation challenges.
Pepsinized cashew proteins elicited weaker allergic reactions than native cashew proteins but importantly retained the ability to stimulate cellular proliferation and cytokine production. Mice sensitized with pepsinized proteins reacted on challenge with native allergens, demonstrating that pepsinized allergens retain immunogenicity in vivo. Immunotherapy with pepsinized cashew allergens significantly decreased allergic symptoms and body temperature decrease relative to placebo after challenge with native and pepsinized proteins.
Immunologic changes were comparable after immunotherapy with native or pepsinized allergens: TH2-type cytokine secretion from splenocytes was decreased, whereas specific IgG1 and IgG2a levels were increased.
Pepsinized cashew proteins are effective in treating cashew allergy in mice and appear to work through the same mechanisms as native protein immunotherapy.
Food allergy; tree nut allergy; cashew; immunotherapy; pepsin; murine model
Food allergy affects 3.9% of US children and is increasing in prevalence. The current standard of care involves avoidance of the triggering food and treatment for accidental ingestions. While there is no current curative treatment, there are a number of therapeutic strategies under investigation. Allergen specific therapies include oral and sublingual immunotherapy with native food protein as well as recombinant food proteins. Allergen non-specific therapies include a Chinese herbal formula (FAHF-2) and the use of anti-IgE monoclonal antibody therapy. Although none of these treatments are ready for clinical use, these therapeutic strategies present promising options for the future of food allergy.
anaphylaxis; desensitization; food allergy; oral immunotherapy; subcutaneous immunotherapy; sublingual immunotherapy; tolerance
In Westernized countries, over 1% of the population is allergic to peanuts or tree nuts, which carries a risk of severe allergic reactions. Several studies support the efficacy of peanut oral immunotherapy (OIT) for reducing the clinical sensitivity of affected individuals; however, the mechanisms of this effect are still being characterized. One mechanism that may contribute is the suppression of effector cells, such as basophils. Basophil anergy has been characterized in vitro as a pathway-specific hyporesponsiveness; however, this has not been demonstrated to occur in vivo.
To evaluate the hypothesis that basophil anergy occurs in vivo due to chronic allergen exposure in the setting of a clinical oral immunotherapy trial.
Samples of peripheral blood were obtained from subjects during a placebo-controlled clinical trial of peanut OIT. Basophil reactivity to in vitro stimulation with peanut allergen and controls was assessed by the upregulation of activation markers, CD63 and CD203c, measured by flow cytometry.
The upregulation of CD63 following stimulation of the IgE receptor, either specifically with peanut allergen or non-specifically with anti-IgE antibody, was strongly suppressed by active OIT. However, OIT did not significantly suppress this response in basophils stimulated by the distinct fMLP receptor pathway. In the subset of subjects with egg sensitization, active peanut OIT also suppressed CD63 upregulation in response to stimulation with egg allergen. Allergen OIT also suppressed the upregulation of CD203c including in response to stimulation with IL-3 alone.
Peanut OIT induces a hyporesponsive state in basophils that is consistent with pathway-specific anergy previously described in vitro. This suggests the hypothesis that effector cell anergy could contribute to clinical desensitization.
human basophils; desensitization; basophil anergy; CD63; CD203c; oral immunotherapy; peanut allergy
Orally administered, food-specific immunotherapy appears effective in desensitizing and potentially permanently tolerizing allergic individuals.
We sought to determine whether milk oral immunotherapy (OIT) is safe and efficacious in desensitizing children with cow’s milk allergy.
Twenty children were randomized to milk or placebo OIT (2:1 ratio). Dosing included 3 phases: the build-up day (initial dose, 0.4 mg of milk protein; final dose, 50 mg), daily doses with 8 weekly in-office dose increases to a maximum of 500 mg, and continued daily maintenance doses for 3 to 4 months. Double-blind, placebo-controlled food challenges; end-point titration skin prick tests; and milk protein serologic studies were performed before and after OIT.
Nineteen patients, 6 to 17 years of age, completed treatment: 12 in the active group and 7 in the placebo group. One dropped out because of persistent eczema during dose escalation. Baseline median milk IgE levels in the active (n = 13) versus placebo (n = 7) groups were 34.8 kUa/L (range, 4.86–314 kUa/L) versus 14.6 kUa/L (range, 0.93–133.4 kUa/L). The median milk threshold dose in both groups was 40 mg at the baseline challenge. After OIT, the median cumulative dose inducing a reaction in the active treatment group was 5140 mg (range 2540-8140 mg), whereas all patients in the placebo group reacted at 40 mg (P = .0003). Among 2437 active OIT doses versus 1193 placebo doses, there were 1107 (45.4%) versus 134 (11.2%) total reactions, with local symptoms being most common. Milk-specific IgE levels did not change significantly in either group. Milk IgG levels increased significantly in the active treatment group, with a predominant milk IgG4 level increase.
Milk OIT appears to be efficacious in the treatment of cow’s milk allergy. The side-effect profile appears acceptable but requires further study.
Cow’s milk; food allergy; IgE; prognosis; desensitization; tolerance; oral immunotherapy
Peanut-specific IgA in saliva correlates with DBPCFC outcomes following peanut SLIT, suggesting that peanut-specific salivary IgA may be a potential biomarker for SLIT used to treat peanut allergy.
Food allergy; peanut allergy; sublingual immunotherapy; saliva; IgA; secretory IgA
Food allergy is increasing in prevalence in westernized countries, leading to significant morbidity including nutritional deficiencies and growth delay as well as psychosocial burdens and the potential for fatal anaphylaxis. There is currently no effective form of therapy, and the mainstay of treatment remains strict avoidance. However, there are a number of promising therapeutic strategies currently being investigated for the treatment of food allergies. Allergen-specific approaches, such as various forms of immunotherapy, have been a major focus of investigation and appear to be promising methods of desensitization. More recently, the addition of anti-IgE monoclonal antibodies (mAbs) to immunotherapy regimens has been studied. Early work with antigen-fixed leukocytes in a murine model has shown promise in inducing tolerance, as have vaccines containing modified recombinant food proteins coadministered with heat-killed Escherichia coli. Nonspecific approaches include a Chinese herbal formulation, anti-IgE mAbs, and Trichuris suis ova therapy. The array of treatment modalities currently being investigated increases the likelihood of finding one or more effective therapies for the treatment of food allergy.
Food allergy; Oral immunotherapy (OIT); Double-blind, placebo-controlled food challenge (DBPCFC); Anti-IgE antibody/omalizumab; Desensitization
To examine circumstances of allergic reactions to foods in a cohort of preschool-aged children.
We conducted a prospective, 5-site observational study of 512 infants aged 3 to 15 months with documented or likely allergy to milk or egg, and collected data prospectively examining allergic reactions.
Over a median follow-up of 36 months (range: 0–48.4), the annualized reaction rate was 0.81 per year (367/512 subjects reporting 1171 reactions [95% confidence interval: 0.76–0.85]). Overall, 269/512 (52.5%) reported >1 reaction. The majority of reactions (71.2%) were triggered by milk (495 [42.3%]), egg (246 [21.0%]), and peanut (93 [7.9%]), with accidental exposures attributed to unintentional ingestion, label-reading errors, and cross-contact. Foods were provided by persons other than parents in 50.6% of reactions. Of 834 reactions to milk, egg, or peanut, 93 (11.2%) were attributed to purposeful exposures to these avoided foods. A higher number of food allergies (P < .0001) and higher food-specific immunoglobulin E (P < .0001) were associated with reactions. Of the 11.4% of reactions (n = 134) that were severe, 29.9% were treated with epinephrine. Factors resulting in undertreatment included lack of recognition of severity, epinephrine being unavailable, and fears about epinephrine administration.
There was a high frequency of reactions caused by accidental and nonaccidental exposures. Undertreatment of severe reactions with epinephrine was a substantial problem. Areas for improved education include the need for constant vigilance, accurate label reading, avoidance of nonaccidental exposure, prevention of cross-contamination, appropriate epinephrine administration, and education of all caretakers.
food allergy; IgE-mediated allergic reaction; epinephrine
Ara h 2 and Ara h 6, co-purified together in a 13-25 kD fraction (Ara h 2/6; 20 kD fraction) on gel filtration chromatography, account for the majority of effector activity in a crude peanut extract (CPE) when assayed with RBL SX-38 cells sensitized with IgE from human peanut allergic sera.
To determine if Ara h 2/6 are the primary peanut allergens responsible for allergic reactions in vivo and to determine if Ara h 2/6 would be sufficient to prevent allergic reactions to a complete CPE.
An oral sensitization mouse model of peanut allergy was used to assess the activity of Ara h 2/6 (20 kD) and CPE without the 20 kD fraction (CPE w/o 20 kD) for allergic provocation challenge and immunotherapy. The activity of these preparations was also tested in an assay of histamine release from human basophils in whole blood.
Compared to mice challenged with control CPE, mice challenged with CPE w/o 20 kD experienced reduced symptoms (p<0.05) and a smaller decrease in body temperature (p<0.01). Results with the basophil histamine release assay corroborated these findings (p<0.01). The mouse model was also used to administer Ara h 2/6 (20 kD) in an immunotherapy protocol, in which peanut-allergic mice treated with the 20 kD fraction experienced significantly reduced symptoms, changes in body temperature, and mast cell protease (MMCP-1) release compared to placebo (p<0.01 for all parameters). Importantly, immunotherapy with the 20 kD fraction was just as effective as treatment with CPE, whereas CPE w/o 20 kD was significantly less effective for higher dose peanut challenges.
Conclusions and Clinical Relevance
Ara h 2/6 are the most potent peanut allergens in vivo and can be used to desensitize peanut-allergic mice. These results have potential implications for clinical research in the areas of diagnosis and immunotherapy for peanut allergy.
Food allergy; peanut allergy; Ara h 2; Ara h 6; desensitization; immunotherapy; human basophil assay; mouse model
Oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) are potential therapies for food allergy, but the optimal method of administration, mechanism of action, and duration of response remain unknown.
We sought to explore the safety and efficacy of OIT and SLIT for the treatment of cow’s milk (CM) allergy.
We randomized children with CM allergy to SLIT alone or SLIT followed by OIT. After screening double-blind, placebo-controlled food challenges and initial SLIT escalation, subjects either continued SLIT escalation to 7 mg daily or began OIT to either 1000 mg (the OITB group) or 2000 mg (the OITA group) of milk protein. They were challenged with 8 g of milk protein after 12 and 60 weeks of maintenance. If they passed the 60-week challenge, therapy was withdrawn, with challenges repeated 1 and 6 weeks later. Mechanistic correlates included end point titration skin prick testing and measurement of CM-specific IgE and IgG4 levels, basophil histamine release, constitutive CD63 expression, CD203c expression, and intracellular spleen tyrosine kinase levels.
Thirty subjects with CM allergy aged 6 to 17 years were enrolled. After therapy, 1 of 10 subjects in the SLIT group, 6 of 10 subjects in the SLIT/OITB group, and 8 of 10 subjects in the OITA group passed the 8-g challenge (P = .002, SLIT vs OIT). After avoidance, 6 of 15 subjects (3 of 6 subjects in the OITB group and 3 of 8 subjects in the OITA group) regained reactivity, 2 after only 1 week. Although the overall reaction rate was similar, systemic reactions were more common during OIT than during SLIT. By the end of therapy, titrated CM skin prick test results and CD63 and CD203c expression decreased and CM-specific IgG4 levels increased in all groups, whereas CM-specific IgE and spontaneous histamine release values decreased in only the OIT group.
OIT was more efficacious for desensitization to CM than SLIT alone but was accompanied by more systemic side effects. Clinical desensitization was lost in some cases within 1 week off therapy.
Food allergy; immunotherapy; milk allergy; basophil; spontaneous histamine release
For egg allergy, dietary avoidance is the only currently approved treatment. We evaluated oral immunotherapy using egg-white powder for the treatment of children with egg allergy.
In this double-blind, randomized, placebo-controlled study, 55 children, 5 to 11 years of age, with egg allergy received oral immunotherapy (40 children) or placebo (15). Initial dose-escalation, build-up, and maintenance phases were followed by an oral food challenge with egg-white powder at 10 months and at 22 months. Children who successfully passed the challenge at 22 months discontinued oral immunotherapy and avoided all egg consumption for 4 to 6 weeks. At 24 months, these children underwent an oral food challenge with egg-white powder and a cooked egg to test for sustained unresponsiveness. Children who passed this challenge at 24 months were placed on a diet with ad libitum egg consumption and were evaluated for continuation of sustained unresponsiveness at 30 months and 36 months.
After 10 months of therapy, none of the children who received placebo and 55% of those who received oral immunotherapy passed the oral food challenge and were considered to be desensitized; after 22 months, 75% of children in the oral-immunotherapy group were desensitized. In the oral-immunotherapy group, 28% (11 of 40 children) passed the oral food challenge at 24 months and were considered to have sustained unresponsiveness. At 30 months and 36 months, all children who had passed the oral food challenge at 24 months were consuming egg. Of the immune markers measured, small wheal diameters on skin-prick testing and increases in egg-specific IgG4 antibody levels were associated with passing the oral food challenge at 24 months.
These results show that oral immunotherapy can desensitize a high proportion of children with egg allergy and induce sustained unresponsiveness in a clinically significant subset. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00461097.)
Data from many studies have suggested a rise in the prevalence of food allergies during the past 10 to 20 years. Currently, no curative treatments for food allergy exist, and there are no effective means of preventing the disease. Management of food allergy involves strict avoidance of the allergen in the patient's diet and treatment of symptoms as they arise. Because diagnosis and management of the disease can vary between clinical practice settings, the National Institute of Allergy and Infectious Diseases (NIAID) sponsored development of clinical guidelines for the diagnosis and management of food allergy. The guidelines establish consensus and consistency in definitions, diagnostic criteria, and management practices. They also provide concise recommendations on how to diagnose and manage food allergy and treat acute food allergy reactions. The original guidelines encompass practices relevant to patients of all ages, but food allergy presents unique and specific concerns for infants, children, and teenagers. To focus on those concerns, we describe here the guidelines most pertinent to the pediatric population.
food allergy; food hypersensitivity; infants; children; guidelines; anaphylaxis
Probiotic administration has been proposed for the prevention and treatment of specific allergic manifestations such as eczema, rhinitis, gastrointestinal allergy, food allergy, and asthma. However, published statements and scientific opinions disagree about the clinical usefulness.
A World Allergy Organization Special Committee on Food Allergy and Nutrition review of the evidence regarding the use of probiotics for the prevention and treatment of allergy.
A qualitative and narrative review of the literature on probiotic treatment of allergic disease was carried out to address the diversity and variable quality of relevant studies. This variability precluded systematization, and an expert panel group discussion method was used to evaluate the literature. In the absence of systematic reviews of treatment, meta-analyses of prevention studies were used to provide data in support of probiotic applications.
Despite the plethora of literature, probiotic research is still in its infancy. There is a need for basic microbiology research on the resident human microbiota. Mechanistic studies from biology, immunology, and genetics are needed before we can claim to harness the potential of immune modulatory effects of microbiota. Meanwhile, clinicians must take a step back and try to link disease state with alterations of the microbiota through well-controlled long-term studies to identify clinical indications.
Probiotics do not have an established role in the prevention or treatment of allergy. No single probiotic supplement or class of supplements has been demonstrated to efficiently influence the course of any allergic manifestation or long-term disease or to be sufficient to do so. Further epidemiologic, immunologic, microbiologic, genetic, and clinical studies are necessary to determine whether probiotic supplements will be useful in preventing allergy. Until then, supplementation with probiotics remains empirical in allergy medicine. In the future, basic research should focus on homoeostatic studies, and clinical research should focus on preventive medicine applications, not only in allergy. Collaborations between allergo-immunologists and microbiologists in basic research and a multidisciplinary approach in clinical research are likely to be the most fruitful.
probiotics; prevention of allergy; pediatric allergy
In the century since Paul Portier and Charles Richet described their landmark findings of severe fatal reactions in dogs re-exposed to venom after vaccination with sea anemone venom, treatment for anaphylaxis continues to evolve. The incidence of anaphylaxis continues to be difficult to measure. Underreporting due to patients not seeking medical care as well as failure to identify anaphylaxis affects our understanding of the magnitude of the disease. Treatment with intramuscular epinephrine continues to be the recommended first line therapy although studies indicate that education of both the patients and the medical community is needed. Adverse food reactions continue to be the leading cause of anaphylaxis presenting for emergency care. Current therapy for food-induced anaphylaxis is built on the foundation of strict dietary avoidance, rapid access to injectable epinephrine, and education to recognize signs and symptoms of anaphylaxis. Investigation into therapy with oral and sublingual immunotherapy as well as other modalities holds hope for improved treatment of food-induced anaphylaxis.
anaphylaxis; food allergy; immunotherapy
Peanut sensitization in diacylglycerol kinase zeta (DGKζ) deficient mice led to elevated peanut-IgE levels and severe anaphylaxis. DGKζ deficient CD4+T cells did not account for the phenotype. Future studies will determine which immune lineage caused increased food hypersensitivity.
Peanut allergy; Diacylglycerolkinase; Toll-like receptor; IgE; Food allergy
Over the past 20 years, food allergy has become an increasingly prevalent international health problem primarily in developed countries. An explanation for this increased prevalence is currently under investigation as it is not well understood. Allergic reactions can result in life threatening anaphylaxis over a short period of time, so the current standard of care dictates strict avoidance of suspected trigger foods and accessibility to injectable epinephrine. Intervention at the time of exposure is considered a rescue therapy rather than a disease modifying treatment. In recent years, investigators have been studying allergen immunotherapy as a way to promote induction of oral tolerance. These efforts have shown some promise towards a viable disease modifying therapy for food allergies. This review will examine the mechanisms of oral tolerance and the breakdown that leads to food allergy, as well as the history and current state of oral and sublingual immunotherapy development.
food allergy; oral tolerance; oral immunotherapy; sublingual immunotherapy
Food allergy; IgE; allergic sensitization; dendritic cells; pathophysiology
There are no treatments currently available for peanut allergy. Sublingual immunotherapy is a novel approach to the treatment of peanut allergy.
To investigate the safety, clinical effectiveness and immunologic changes with sublingual immunotherapy in peanut-allergic children.
In this double-blind, placebo-controlled study, subjects underwent 6 months of dose escalation and 6 months of maintenance dosing followed by a double-blind, placebo-controlled food challenge.
Eighteen children ages 1 to 11 years completed 12 months of dosing and the food challenge. Dosing side effects were primarily oropharyngeal and uncommonly required treatment. During the double-blind, placebo-controlled food challenge, the treatment group safely ingested 20 times more peanut protein than the placebo group (median 1710 mg vs. 85 mg, p=0.011). Mechanistic studies demonstrated a decrease in prick skin test wheal size (p=0.020) and decreased basophil responsiveness after stimulation with 10−2 mcg/ml (p=0.009) and 10−3 mcg/ml (p=0.009) of peanut. Peanut-specific IgE increased over the initial 4 months (p=0.002) then steadily decreased over the remaining 8 months (p=0.003) while peanut-specific IgG4 increased during the 12 months (p=0.014). Lastly, IL-5 levels decreased after 12 months (p=0.015). No statistically significant changes were found in IL-13 levels, the percent of T regulatory cells, or IL-10 and IFN-gamma production.
Peanut sublingual immunotherapy is able to safely induce clinical desensitization in peanut allergic children with evidence of immunologic changes suggesting a significant change in the allergic response. Further study is required to determine if continued peanut sublingual immunotherapy is able to induce long-term immune tolerance.
peanut allergy; sublingual immunotherapy; desensitization; food allergy
Open-label oral immunotherapy (OIT) protocols have been used to treat small numbers of patients with peanut allergy. Peanut OIT has not been evaluated in double-blind, placebo-controlled trials.
To investigate the safety and effectiveness of OIT for peanut allergy in a double blind, placebo-controlled study.
In this multicenter study, peanut-allergic children ages 1-16 years received OIT with peanut flour or placebo. Initial escalation, build-up, and maintenance phases were followed by an oral food challenge at approximately one year. Titrated skin prick tests (SPT) and laboratory studies were performed at regular intervals.
Twenty-eight subjects were enrolled in the study. Three peanut OIT subjects withdrew early in the study due to allergic side effects. During the double-blind, placebo-controlled food challenge, all remaining peanut OIT subjects (N=16) ingested the maximum cumulative dose of 5000 mg (approximately 20 peanuts), while placebo subjects (N=9) ingested a median cumulative dose of 280 mg (range, 0-1900 mg) [p<0.001]. In contrast to the placebo group, the peanut OIT group showed reductions in SPT size (p<0.001), IL-5 (p=0.01), and IL-13 (p=0.02) and increases in peanut-specific IgG4 (p<0.001). Peanut OIT subjects had initial increases in peanut-specific IgE (p<0.01) but did not show significant change from baseline by the time of OFC. The ratio of FoxP3 hi: FoxP3 intermediate CD4+CD25+ T cells increased at the time of OFC (p=0.04) in peanut OIT subjects.
These results conclusively demonstrate that peanut OIT induces desensitization and concurrent immune modulation. The present study continues and is evaluating the hypothesis that peanut OIT causes long-term immune tolerance.
peanut allergy; oral immunotherapy; desensitization; food allergy
The intestine has an unenviable task: to identify and respond to a constant barrage of environmental stimuli that can be both dangerous and beneficial. The proper execution of this task is central to the homeostasis of the host, and as a result the gastrointestinal tract contains more lymphocytes than any other tissue compartment in the body, as well as unique antigen presenting cells with specialized functions. When antigen is initially encountered through the gut, this system generates a robust T-cell mediated hyporesponsiveness called oral tolerance. Although seminal observations of oral tolerance were made a century ago, the relevant mechanisms are only beginning to be unraveled with the use of modern investigational techniques. Food allergy is among the clinical disorders that occur from a failure of this system, and therapies that seek to reestablish tolerance are currently under investigation.
oral tolerance; T regulatory cell; Foxp3; dendritic cell; food allergy; microbiota; vitamin A; TGF-β; CD103
Peanut allergy is typically severe, life-long and prevalent.
To identify factors associated with peanut sensitization.
We evaluated 503 infants 3–15 months of age (mean, 9.4 months) with likely milk or egg allergy but no previous diagnosis of peanut allergy. A total of 308 had experienced an immediate allergic reaction to cow’s milk and/or egg and 204 had moderate to severe atopic dermatitis and a positive allergy test to milk and/or egg. A peanut IgE level of ≥ 5 kUA/L was considered likely indicative of peanut allergy.
A total of 140 (27.8%) infants had PN-IgE levels ≥5 kUA/L. Multivariate analysis including clinical, laboratory and demographic variables showed frequent peanut consumption during pregnancy (OR 2.9, 95% CI 1.7–4.9, p < 0.001), IgE levels to milk (p = 0.001) and egg (p < 0.001), male sex (p = 0.02) and non-white race (p = 0.02) to be the primary factors associated with peanut IgE ≥5 kUA/L. Frequency of peanut consumption during pregnancy and breast feeding showed a dose-response association with peanut IgE ≥ 5 kUA/L, but only consumption during pregnancy was a significant predictor. Among 71 infants never breastfed, frequent consumption of peanut during pregnancy was strongly associated with peanut IgE ≥ 5 kUA/L (OR-4.99, 95% CI-1.69–14.74, p < 0.004).
In this cohort of infants with likely milk or egg allergy, maternal ingestion of peanut during pregnancy was strongly associated with a high level of peanut sensitization.
food allergy; sensitization; atopy; peanut allergy