Immunoglobulin E-mediated Food Allergy Research Articles

Innate lymphoid cells in immunoglobulin E-mediated food allergy.

Recognition of the importance of innate lymphoid cells (ILCs) in the immune mechanisms of food allergy has grown in recent years. This review summarizes recent findings of ILCs in immunoglobulin E (IgE)-mediated food allergy. New research on ILCs in the context of the microbiome and other atopic diseases are also considered with respect to how they can inform understanding of the role of ILCs in food allergy. ILCs can mediate allergic and tolerogenic responses through multiple pathways. A novel subset of interleukin (IL)-10 producing ILC2s are associated with tolerance following immunotherapy to grass pollen, house dust mite allergy and lipid transfer protein allergy. ILC2s can drive food allergen-specific T cell responses in an antigen-specific manner. A memory subset of ILC2s has been identified through studies of other atopic diseases and is associated with effectiveness of response to therapy. The role of ILCs in food allergy and oral tolerance is relatively understudied compared to other diseases. ILCs can modulate immune responses through several mechanisms, and it is likely that these are of importance in the context of food allergy. Better understanding of theses pathways may help to answer fundamental questions regarding the development of food allergy and lead to novel therapeutic targets and treatment.

Navigating the landscape of food allergies: Insights and perspectives from the AMCP Market Insights Program.

AMCP convened a panel of clinical and managed care experts to identify insights regarding the prevalence, clinical manifestations, and management approaches for immunoglobulin E-mediated food allergies. This article aims to summarize expert perspectives on health care system challenges and areas of agreement concerning the management of food allergies, and to advance payers' understanding of their role in supporting health care for patients with food allergies. Food allergy management requires dietary modification and is associated with significant patient and caregiver burdens. Emerging therapies provide hope for those living with food allergies but will likely lead to a rise in health plan pharmacy expenses. In considering the value of new treatments, it is important to consider the total cost of care and the value of preventing anaphylaxis and enhancing the patient's quality of life. Several challenges remain in identifying the appropriate patient population for treatment with newer agents and in optimizing treatment outcomes. Addressing health disparities will require standardized clinical protocols, better access to specialized allergy care, and management of comorbid conditions.

Evaluation of atopic diseases in patients with allergic contact dermatitis.

Background: There is controversy on whether allergic contact dermatitis (ACD) is associated with atopy. Research on eczema and the risk of ACD is mixed, and there is sparse literature on other atopic conditions. Objective: Our study examined the prevalence of several atopic conditions, including allergic rhinitis, eczema, asthma, and food allergies in patients with ACD, and compared these to patients without ACD. Methods: We retrospectively reviewed adult patients ages ≥ 18 years with ACD (n = 162) with positive patch testing results and documented any history of atopy, including childhood eczema, asthma, allergic rhinitis, and immunoglobulin E-mediated food allergy. The prevalence of atopic conditions was compared between our ACD cohort and controls without ACD (n = 163) from our electronic medical records system (age and gender matched). Results: Among our patients with ACD, 53 (33%) had allergic rhinitis, 22 (14%) had childhood eczema, 32 (20%) had asthma, and 8 (5%) had food allergies. We observed that the odds of atopy overall (n = 76) in the ACD group compared with the control group were increased (odds ratio [OR] 1.88; p = 0.007). Allergic rhinitis was the highest risk factor (n = 53) with an OR of 12.64 (p < 0.001). Childhood eczema (n = 22) was also increased in the ACD group (OR 2.4; p = 0.026). The odds of asthma and food allergy in the ACD group were also increased; however, the difference was not statistically significant from the control group (OR 1.76 [p = 0.071] and OR 2.76 [p = 0.139], respectively). Conclusion: Patients with ACD had increased odds of eczema, allergic rhinitis, and atopic conditions overall. Asthma and food allergies were not found to have a statistically significant correlation. Larger studies that delve into atopic risk factors in ACD would be important to confirm these findings.

Omalizumab for the reduction of allergic reactions to foods: a narrative review.

The frequency of food allergies varies between 2% and 10%, depending on characteristics including age, region, race, and method of diagnosis self-reported by patients or oral food challenges (OFCs). The most common allergies reported are tree nuts (1.2%), milk (1.9%), peanuts (2.2%), and shellfish (1.3%). Omalizumab injection has now been approved by the FDA for the treatment of immunoglobulin E-mediated food allergies in specific adults and children aged one year or older. This medication reduces the risk of allergic reactions (Type I), which can include anaphylaxis, when an individual accidentally encounters one or more food allergens. Omalizumab functions by binding to IgE and altering IgE-mediated pathways, which lessens IgE's capacity to cause allergic reactions. Promising outcomes from clinical trials and case studies include lowered anaphylactic risk and enhanced tolerance to allergens. Omalizumab, however, may have adverse effects; thus, close observation is required. Overall, this review sheds light on the efficacy, safety, and clinical implications of omalizumab, highlighting its potential as a useful intervention for IgE-mediated food allergies.

Low-dose oral immunotherapy in immunoglobulin E-mediated food allergies.

Nowadays, the management of food allergies has increasingly moved from conventional oral immunotherapy (OIT) to low-dose OIT or low-dose OIT utilizing hypoallergenic foods. This shift is largely because the latter appears to induce oral tolerance with fewer adverse effects than the former. However, the mechanisms underpinning such differences remain unclear. To better understand these mechanisms, we conducted a comparative study scrutinizing the mechanisms of OIT, especially those of low-dose desensitization. We also summarized articles on low-dose OIT and low-dose OIT using hypoallergenic foods. We examined the efficacy, safety, and immunological parameters of low-dose OIT and those of low-dose OIT with hypoallergenic foods with the aim of shedding some light on low-dose OIT and its therapeutic application in inducing oral tolerance for individuals with food allergies.

Food oral immunotherapy and eosinophilic esophagitis: Complication or comorbidity?

Oral immunotherapy (OIT) is a treatment for immunoglobulin E-mediated food allergy (IgE-FA) where patients consume increasing amounts of food they are allergic to, reducing sensitivity. Allergens treated with OIT include cow milk (CM), egg, and lipid transfer protein (LTP). LTPs are the primary cause of food allergy in adults in Mediterranean European countries

Patterns in the Development of Pediatric Allergy.

Describe clinical and epidemiologic patterns of pediatric allergy using longitudinal electronic health records (EHRs) from a multistate consortium of US practices. Using the multistate Comparative Effectiveness Research through Collaborative Electronic Reporting EHR database, we defined a cohort of 218 485 children (0-18 years) who were observed for ≥5 years between 1999 and 2020. Children with atopic dermatitis (AD), immunoglobulin E-mediated food allergy (IgE-FA), asthma, allergic rhinitis (AR), and eosinophilic esophagitis (EoE) were identified using a combination of diagnosis codes and medication prescriptions. We determined age at diagnosis, cumulative incidence, and allergic comorbidity. Allergic disease cumulative (and peak age of) incidence was 10.3% (4 months) for AD, 4.0% (13 months) for IgE-FA, 20.1% (13 months) for asthma, 19.7% (26 months) for AR, and 0.11% (35 months) for EoE. The most diagnosed IgE-FAs were peanut (1.9%), egg (0.8%), and shellfish (0.6%). A total of 13.4% of children had ≥2 allergic conditions, and respiratory allergies (ie, asthma, AR) were commonly comorbid with each other, and with other allergic conditions. We detail pediatric allergy patterns using longitudinal, health care provider-based data from EHR systems across multiple US states and varied pediatric practice types. Our results support the population-level allergic march progression and indicate high rates of comorbidity among children with food and respiratory allergies.

Early Introduction of Allergenic Foods in Infants and Children

Immunoglobulin E-mediated food allergies are a concerning health problem affecting 5.5% of children and 6% of adults in the United States. Nine foods cause 90% of food allergies, with milk, eggs, and peanuts most often linked to food allergies in infants and children. Prevention strategies have shifted from avoidance of foods to the early introduction of high allergenic foods. Evidence supports that the early introduction of peanuts can reduce food allergies. United States guidelines promote the optimal times for the introduction of high-allergen foods. Future research is required to ensure evidence-based best practices for patients and families.

Does maternal fermented dairy products consumption protect against cow's milk protein allergy in toddlers?

BackgroundCow's milk protein allergy (CMPA) is the most common immunoglobulin E-mediated food allergy in childhood. ObjectiveTo investigate the potential impact on the disease of the frequency, amount, and diversity of maternal consumption of fermented dairy products (FDP) during pregnancy and lactation in children with immunoglobulin E-mediated CMPA. MethodsOne hundred sixty toddlers (80 with physician-diagnosed CMPA and 80 healthy controls) and their mothers participated in this case-control study. The data were collected using a structured questionnaire and were compared between the 2 groups. ResultsThe most commonly consumed FDP were cheese, yogurt, and tarhana. The amounts of maternal yogurt, tarhana, and kefir consumed during pregnancy (P < .001, P < .001, and P = .04, respectively) in addition to yogurt and tarhana consumption during lactation (P < .001 and P = .001, respectively) were lower in toddlers with CMPA. The frequency of maternal consumption of yogurt, cheese, and tarhana during lactation (P = .001, P = .003, and P = .02, respectively) and the diversity of FDP were also lower in toddlers with CMPA (P = .001). At multivariate logistic regression analysis, maternal weight gain during pregnancy (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.04-1.18; P = .001), maternal age (OR, 1.20; 95% CI, 1.09-1.31; P < .001), and gestational age at birth (OR, 1.23; 95% CI, 1.03-1.48; P = .02) increased the odds of the baby having CMPA. The diversity of FDP consumed during lactation was protective against CMPA (OR, 0.439; 95% CI, 0.272-0.711; P = .001). ConclusionWeekly maternal consumption of FDP was low during pregnancy and lactation in toddlers with CMPA. Although the diversity of FDP consumed during lactation may reduce the risk of CMPA, this effect was not observed during pregnancy.

Skin care interventions in infants for preventing eczema and food allergy.

Skin care interventions in infants for preventing eczema and food allergy.

Transient acquired donor peanut allergy presenting as life-threatening anaphylaxis following lung transplantation

Transient acquired donor immunoglobulin (Ig)E-mediated food allergy after solid organ transplantation (SOT) has been described in a few case reports and in 1 systematic review. Theories regarding mechanism range from passive transfer of allergen-specific IgE through sensitized donor mast cells, 1 Castells M Boyce J. Transfer of peanut allergy by a liver allograft. N Engl J Med. 1998; 338: 202-203 Crossref PubMed Scopus (15) Google Scholar to transfer of B lymphocytes producing allergen-specific IgE or allergen-specific Th2 lymphocytes into the circulation at the time of transplantation. 2 Legendre C Caillat-Zucman S Samuel D Morelon S Bismuth H Bach J et al. Transfer of symptomatic peanut allergy to the recipient of a combined liver and kidney transplant. N Engl J Med. 1997; 337: 822-824 Crossref PubMed Scopus (137) Google Scholar

Optimal patient selection for oral immunotherapy.

Standard criteria for ideal patient selection with food oral immunotherapy (OIT) have yet to be determined. Although there are a handful of contraindications to consider before recommending OIT, most patients with confirmed immunoglobulin E-mediated food allergies are appropriate candidates. Success rates of OIT can vary widely and be influenced by several factors. Choosing the most appropriate candidate for an OIT program can mitigate risks and provide the best chance for patients to be successful.

Identification of IgE-Mediated Food Allergy and Allergens in Older Children and Adults with Asthma and Allergic Rhinitis

Prevalence of immunoglobulin (Ig) E-mediated food allergy is primarily reported for certain pediatric populations and adults. The present study was aimed to investigate the relative prevalence of food allergy and allergens in older children and adults with asthma and allergic rhinitis. Patients (12-62 years) were screened using standard questionnaire and skin prick-test (SPT) with common foods and aeroallergens. Specific IgE level was determined by enzyme linked immunosorbent assay (ELISA) and allergy was established by blinded food challenges. Of 1860 patients screened, 1097 (58.9%) gave history of food allergy. Of the history positive patients skin tested (n=470), 138 (29.3%) showed a marked positive reaction to food extracts. Rice elicited positive SPT reaction in maximum number of cases 29 (6.2%) followed by blackgram 28 (5.9%), lentil 26 (5.5%), citrus fruits 25 (5.3%), pea 18 (3.8%), maize 18 (3.8%) and banana 17 (3.6%). The SPT positive patients showed elevated specific IgE levels (range: 0.8-79 IU/mL) against respective food allergens than normal controls (0.73 IU/mL, mean +/- 2 SD). Food allergy was confirmed in 21/45 (46.6%) of the patients by blinded controlled food challenges. The prevalence of food allergy was estimated to be 4.5% (2.6%-6.34%) at 95% confidence interval (95% CI) in test population (n=470). Sensitisation to food was significantly associated with asthma (p = 0.0065) while aeroallergens were strongly related to rhinitis (p < 0.01). Food allergy is estimated to be 4.5% in adolescents and adults with asthma, rhinitis or both. Rice, citrus fruits, blackgram and banana are identified as major allergens for inducing allergic symptoms.

Should children with immunoglobulin E–mediated food allergy be screened for eosinophilic esophagitis?

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus, involving an allergen-mediated process highly associated with other atopic conditions.1–3 Several studies have identified the significance of food antigens underlying EoE development, evidenced by treatment using food elimination diets and the emergence of EoE with oral immunotherapy.4,5 The progression from immunoglobulin E–mediated food allergy (IgE-FA) to EoE has been illustrated, either from the same or different food triggers.

Risk Factors for the Development of IgE-Mediated Food Allergy in Preschool Children with Asthma.

Food allergy is a component of the atopic march and may have effects on asthma. This study aimed to evaluate the risk factors for confirmed immunoglobulin E-mediated food allergies and their impact on the clinical picture in preschool children with asthma. Clinical history and allergic assessment results were obtained from medical records and analyzed retrospectively. Preschool children with asthma were included in the study and the characteristics of food allergy and asthma were evaluated. The patients were grouped as those with food allergy (Group I, n = 60) and those without (Group II, n = 98). In patients with food allergy and asthma, the number of episodes requiring systemic steroids in the last year (p = 0.002), atopic dermatitis (p = 0.001), parental atopic disease (p = 0.009) and aeroallergen sensitivity rates (p < 0.001) was higher than patients without food allergies. The use of medium or high doses of inhaled steroids to achieve asthma control was more frequent in patients with food allergies (p = 0.014). Parental history of atopic disease [p = 0.007, odds ratio (OR): 3.27, 95% confidence interval (CI) 1.37-7.77)], atopic dermatitis (p = 0.017, OR: 2.80, 95% CI: 1.19-6.57), starting complementary food after 6 months (p = 0.004, OR: 3.9, 95% CI: 1.5-10.0) and having aeroallergen sensitivity (p < 0.001, OR: 6.01, 95% CI: 2.21-16.29) were identified as significant risk factors for food allergy. Asthmatic preschool children with food allergies are more likely to have a parental atopic disease, atopic dermatitis, aeroallergen sensitivity and starting complementary food after 6 months. These patients experience more asthma attacks and need higher doses of steroids.

Infant gut bacterial community composition and food-related manifestation of atopy in early childhood.

Background:Immunoglobulin E–mediated food allergy (IgE-FA) has emerged as a global public health concern. Immune dysregulation is an underlying mechanism for IgE-FA, caused by “dysbiosis” of the early intestinal microbiota. We investigated the association between infant gut bacterial composition and food-related atopy at age 3–5 years using a well-characterized birth cohort.Methods:The study definition of IgE-FA to egg, milk, or peanut was based on physician panel retrospective review of clinical and questionnaire data collected from birth through age 3–5 years. Using 16S rRNA sequencing, we profiled the bacterial gut microbiota present in stool specimens collected at 1 and 6 months of age.Results:Of 447 infants with data for analysis, 44 (9.8%) met physician panel review criteria for IgE-FA to ≥1 of the three allergens. Among children classified as IgE-FA at 3–5 years, infant stool samples showed significantly less diversity of the gut microbiota compared with the samples of children classified as no IgE-FA at age 3–5 years, especially for milk and peanut (all covariate-adjusted p’s for alpha metrics <.007). Testing of individual operational taxonomic units (OTUs) revealed 6-month deficiencies in 31 OTUs for IgE-FA compared with no IgE-FA, mostly in the orders Lactobacillales, Bacteroidales, and Clostridiales.Conclusions:Variations in gut microbial composition in infant stool were associated with a study definition of IgE-FA at 3–5 years of age. This included evidence of a lack of bacterial diversity, deficiencies in specific OTUs, and delayed microbial maturation. Results support dysbiosis in IgE-FA pathogenesis.

Increased IgE-Mediated Food Allergy With Food Protein-Induced Allergic Proctocolitis

To examine the relationship between food protein-induced allergic proctocolitis (FPIAP) and the risk of developing immunoglobulin E–mediated food allergy (IgE-FA) in infants.In the study, the researchers included 903 infants who were enrolled in the Gastrointestinal Microbiome and Allergic Proctocolitis (GMAP) cohort, an observational healthy-infant cohort study in which researchers characterized the epidemiology of FPIAP in the primary care setting.Infants diagnosed with FPIAP with presence of documented blood in the stool were included. IgE-FA was determined by 2 allergists independently reviewing clinical and sensitization data from children whose parents reported suspect reactions and included if both reviewers agreed the diagnosis was “confirmed” or probable.” The rate of IgE-FA was compared between healthy infants and those with FPIAP. Additional variables, including the presence of eczema, were evaluated by using univariable and multivariable logistic regression.More children with FPIAP developed IgE-FA (11%), compared with healthy children (5%). Adjusting for eczema, children with FPIAP had twice the odds of developing IgE-FA to any food. FPIAP was most strongly associated with IgE-FA to milk, although the study was not powered to detect relationships to individual foods.Children with FPIAP were at an increased risk for having IgE-FA. This may be multifactorial, including shared pathogenesis in the development of FPIAP and IgE-FA and/or an effect of antigen elimination diet used to treat FPIAP.FPIAP is a common diagnosis early in infancy that is benign and self-resolved. However, a diagnosis of FPIAP often leads to prolonged dietary restriction from cow’s milk (the most common cause) and potentially soy protein as well. Although conventional teaching is to wait until 12 months of age to reintroduce dairy to infants with FPIAP, it can likely be introduced much earlier. In this study, researchers found an association between a diagnosis of FPIAP with increased risk for IgE-FA, although diagnosis was not confirmed through oral food challenges. Although the authors report some potential common immunologic pathways between FPIAP (a non–immunoglobulin E–mediated food reaction) and IgE-FA, a true causative effect has not been established. Now that current evidence-based guidelines recommend early introduction of allergenic foods to all infants (beginning ∼4-6 months of age) and ongoing inclusion in the diet as the best path toward food allergy prevention, with this study, the authors reinforce the need for pediatricians to discuss these guidelines with parents. This is especially true in infants at a higher risk to develop food allergy, including those with severe or persistent atopic dermatitis and now, potentially, other forms of non–immunoglobulin–mediated food allergy. Now, more than ever, we need to let the infants eat!

Provider Recommendations and Maternal Practices When Providing Breast Milk to Children With Immunoglobulin E-Mediated Food Allergy

To evaluate health care provider recommendations and the breastfeeding dietary practices of mothers with a child who has immunoglobulin E (IgE)-mediated food allergy.The study participants were recruited from online social media groups for breastfeeding mothers or mothers of children with food allergies.The study included a Web-based survey with the following initial questions as inclusion criteria: having a child diagnosed with an IgE-mediated food allergy by a health care provider before 2 years of age, confirmation of food allergy with blood or skin testing, listing of specific food(s) to which the child is allergic in the survey, confirmation of food allergy by an allergist, and consumption of breast milk before the child’s diagnosis. With the survey, the researchers then explored the mother’s consumption of food to which the child has an allergy (while breastfeeding), and, if present, reported possible allergic reactions were rated by a board-certified allergist on a scale of 1 (highly inconsistent) to 5 (highly consistent) with an IgE-mediated reaction.A total of 133 mothers completed the survey. A total of 47.4% (n = 63) of mothers reported their health care provider encouraged them to continue breastfeeding without dietary restrictions, 17.3% (n = 23) were advised to continue breastfeeding but avoid eating the food(s) their child has an allergy to, and 28.6% (n = 38) stated this issue was not addressed. A total of 88% (n = 117) of mothers noticed no allergic reaction in their child while consuming the food their child has an allergy to, and 12% (n = 16) believed their child had a possible allergic reaction. Of the 16 who reported reactions, only 4 were “likely consistent” with an IgE-mediated reaction, most of which were mild. The remaining reported reactions were inconsistent with an IgE-mediated reaction. All 4 mothers completely eliminated the food(s) from their own diet while continuing to breastfeeding their child.This study reveals the inconsistencies in counseling provided by health care providers to breastfeeding mothers of children with IgE-mediated food allergy. Most mothers were able to consume the food their child was allergic to while breastfeeding without adverse sequelae.With this study, the authors highlight the need for further research and unification of recommendations provided to breastfeeding mothers of children with food allergies. Strict avoidance of food allergens by breastfeeding mothers may not be warranted. If reactions are reported, a thorough history should be performed to determine if it is consistent with an IgE-mediated reaction before recommending avoidance in the mother’s diet.

A Systematic Review of Metabolic Alterations Underlying IgE-Mediated Food Allergy in Children.

Immunoglobulin E-mediated food allergies (IgE-FA) are characterized by an ever-increasing prevalence, currently reaching up to 10.4% of children in the European Union. Metabolomics has the potential to provide a deeper understanding of the pathogenic mechanisms behind IgE-FA. In this work, literature is systematically searched using Web of Science, PubMed, Scopus, and Embase, from January 2010 until May 2021, including human and animal metabolomic studies on multiple biofluids (urine, blood, feces). In total, 15 studies on IgE-FA are retained and a dataset of 277 potential biomarkers is compiled for in-depth pathway mapping. Decreased indoleamine 2,3-dioxygenase-1 (IDO- 1) activity is hypothesized due to altered plasma levels of tryptophan and its metabolites in IgE-FA children. In feces of children prior to IgE-FA, aberrant metabolization of sphingolipids and histidine is noted. Decreased fecal levels of (branched) short chain fatty acids ((B)SCFAs) compel a shift towards aerobic glycolysis and suggest dysbiosis, associated with an immune system shift towards T-helper 2 (Th2) responses. During animal anaphylaxis, a similar switch towards glycolysis is observed, combined with increased ketogenic pathways. Additionally, altered histidine, purine, pyrimidine, and lipid pathways are observed. To conclude, this work confirms the unprecedented opportunities of metabolomics and supports the in-depth pathophysiological qualification in the quest towards improved diagnostic and prognostic biomarkers for IgE-FA.

Differentiation of food protein-induced enterocolitis syndrome misleading to necrotizing enterocolitis

BackgroundFood protein-induced enterocolitis syndrome (FPIES) is a rare non–immunoglobulin E-mediated food allergy with necrotizing enterocolitis (NEC)-like symptoms which requires differential diagnosis as treatments differ. ObjectiveTo evaluate the clinical, laboratory, and radiologic findings that differentiate FPIES from NEC in preterm and term infants. MethodsClinical features, comorbidities, and laboratory and radiologic findings of neonates with presumed NEC were reviewed retrospectively and compared between FPIES and NEC in preterm and term infants who were admitted to the neonatal intensive care unit at Seoul National University Bundang Hospital between May 2003 and February 2020. ResultsA total of 10 of 150 (6.7%) preterm and 17 of 38 (44.7%) term infants with presumed NEC were confirmed to have FPIES; the remainder had NEC by modified Bell's criteria. Demographics and comorbidities were similar between these groups. Symptoms such as hematochezia, shock, leukocytosis, peripheral eosinophilia, and feeding of extensively hydrolyzed milk formula or elemental formula after discharge were significantly different between the 2 groups in term infants (P <.05), but not in preterm infants. On abdominal ultrasonography, pneumatosis intestinalis was more common among preterm FPIES (44.4%) than NEC cases (21.6%) (P =.04). Among the preterm infants, 4 FPIES (40%) and 25 NEC (17.9%) cases required surgery (P =.10). ConclusionDifferentiating FPIES in neonates suspected of having NEC is important as dietary elimination of the triggering milk protein can be recommended instead of prolonged fasting and antibiotic treatment, which are indicated for NEC, in both term and preterm infants.