Development Of Food Allergy Research Articles

RACIAL DIFFERENCES IN FOOD ALLERGY DIAGNOSIS AMONG CHILDREN WITH ATOPIC DERMATITIS INDEPENDENT OF SOCIOECONOMIC CONDITION

<h3>Introduction</h3> It is well-known that children with atopic dermatitis are at increased risk of developing food allergy. To deepen this understanding, we explored the possible association of race and socioeconomic condition with diagnosis of food allergy in children with atopic dermatitis. <h3>Methods</h3> We conducted a large single-center retrospective cohort study of children aged 0-18 years with atopic dermatitis to determine whether each child had a food allergy diagnosis. We performed logistic regression, adjusting for age, race, sex, BMI, and indicators of socioeconomic condition [insurance status and Area Deprivation Index (ADI)]. <h3>Results</h3> Among the 4,322 children analyzed for this study, 16% were Non-Hispanic White, 39% Black, 33% Hispanic, and 6% Asian. Compared with non-Hispanic White children with atopic dermatitis, Hispanic children with atopic dermatitis were significantly less likely to have a food allergy diagnosis (OR=0.774, 95% CI [0.689-0.983], p=0.036). Conversely, both Black children and Asian children with atopic dermatitis were more likely to have been diagnosed with food allergy (OR=1.293, 95% CI [1.109-1.642], p=0.035 and OR=1.493, 95% CI [1.075-2.073], p=0.017 respectively). Age, male gender, non-Medicaid insurance, and lower area deprivation (higher socioeconomic condition) were all statistically significantly associated with increased risk of food allergy diagnosis. <h3>Conclusion</h3> The association between race/ethnicity and risk of food allergy diagnosis among children with atopic dermatitis persisted after thoroughly adjusting for socioeconomic condition using two different markers (insurance status and ADI). Clearly defining which children with atopic dermatitis are at highest risk of developing food allergies can help inform future efforts in early food allergy diagnosis and prevention.

THE ROLE OF SKIN CARE PRODUCTS AND EARLY FOOD FOR THE PREVENTION OF ATOPIC DERMATITIS IN INFANTS

The aim of the study&#x0D; The aim of this study was to assess the value of interventions aimed at improving the skin barrier and skin care products, as well as breastfeeding and early introduction of complementary foods, for the primary prevention of atopic dermatitis (AD) and food allergy in infants.&#x0D; Materials and methods&#x0D; We started a survey in the period from May 2022, which continues to this day. The survey was conducted with the help of Google forms and distributed on the Internet, as well as parents of children who applied for help at Kyiv children’s clinical hospital No. 2 and MC "Allergolog" were interviewed. The relationship between intervention methods and the development of AD and food allergy was determined using the odds ratio (OR) with a 95% confidence interval (CI).&#x0D; Results&#x0D; According to the survey data, 42,2% of children received moisturizing cream, parents of 16,5% of children reported using moisturizing oil for bathing the child, 12,4% of parents used less soap and bathed the child less often, 28,9% reported that they did not use none of these methods and means of care.&#x0D; AD occurred in 23,7% of children interviewed. The odds ratio for the moisturizing cream group was 68,6 (CI 3,9-1201,5), p=0,004, for the groups that used moisturizing oils for bathing – 8,9 (CI 0,4-197,6), p= 0,17, for the group where the intervention was a reduction in bathing and using soap – 7,1 (CI 0,3-186,0), p=0,24.&#x0D; 18,6% of respondents reported a reaction to food that occurred in the child within 2 hours after consumption. We have not found any role of emollients (OR=1,4, CI 0,4-4,9), p=0,56, moisturizing oils for bathing (OR=0,3, CI 0,03-2,6), p=0,27, and reduced use of soap and water (OR=1,4 (CI 0,3-7,2), p=0,66 for the development of food allergy.&#x0D; The duration of breastfeeding (more than 3 months) did not affect the risk of developing AD (OR = 0,1, CI 0,01-2,6), p = 0,19, or food allergy (OR = 1,3, CI 0,3-6,9), p=0,74. Also, the role of earlier introduction of supplementary food on the development of AD and food allergy was not shown: the OR for AD was 0,9 (CI 0,3-2,7), p=0,8, the OR for food allergy was 0,8 (CI 0,2- 2,9), p=0,76.&#x0D; Conclusions&#x0D; This study did not reveal the protective role of skin care products, breastfeeding, and early introduction of complementary foods for the development of AD and food allergies in children. A larger survey will allow us to study the effect of emollients and other preventive measures on the development of food allergies in a group of children with AD.

Therapeutic approach to atopic dermatitis in children

Background: Atopic dermatitis, a chronic inflammatory skin disease can significantly reduce patients’ quality of life. It is commonly observed in infants or young children but can also occur in adults. Patients with atopic dermatitis are at risk of developing food allergies, allergic rhinitis, and asthma.Current Concepts: Treatment of atopic dermatitis should commence with moisturization of epidermal skin and avoidance of environmental factors that may trigger exacerbation of atopic dermatitis. Topical corticosteroid application remains the gold standard for medical management of atopic dermatitis; however, topical corticosteroids are often avoided owing to concerns regarding the adverse effects of these drugs. Recently, several systemic immunosuppressants and biological agents have been introduced for the treatment of atopic dermatitis. These medications are associated with fewer adverse effects than those observed with previous treatments and have therefore shown positive results for successful management of atopic dermatitis.Discussion and Conclusion: It is expected that new drugs tailored to the disease level of each patient will revolutionize the treatment of atopic dermatitis more effectively in future.

Spi-B alleviates food allergy by securing mucosal barrier and immune tolerance in the intestine.

Food allergy is a type I allergic reaction induced by mast cells and is mainly activated by allergen-specific immunoglobulin (Ig)E. Spi-B is an E26-transformation-specific (Ets) family transcription factor essential for the differentiation and functional maturation of several immune cell subsets, including mast cells. However, the possible involvement of Spi-B in food allergy remains unclear. In this study, we found that Spi-B-deficient mice were highly susceptible to food allergy to ovalbumin (OVA), as indicated by the exacerbation of diarrhea and elevation of serum IgE levels. These pathological changes were associated with enhanced mast cell infiltration into the intestinal lamina propria. Activation of mast cells in the intestinal mucosa was observed in Spib−/− mice, even under physiological conditions. Accordingly, Spi-B deficiency increased the translocation of fluorescently labeled dextran from the lumen to the serum, suggesting increased intestinal permeability in Spib−/− mice. Moreover, Spib−/− mice showed defects in oral tolerance induction to OVA. These data illustrate that Spi-B suppresses the development of food allergies by controlling the activation of intestinal mast cells and by inducing immune tolerance to food allergens.

The role of TLR-3 in the course and outcomes of rotavirus infection in infants

It was found that the clinical picture of rotavirus infection in infants with an initially low number of immunocompetent cells expressing TLR-3 does not differ significantly from that of patients with an initially large number of cells expressing TLR-3. When analyzing the treatment, it turned out that antibacterial therapy due to the activation of bacterial microflora was used only in children with an initially low number of immunocompetent cells expressing TLR-3. In the same group of patients, the development of atopic dermatitis and food allergies was noted during catamnestic observation for 6—12 months after rotavirus infection.

SIGNIFICANCE OF TOLL-LIKE RECEPTOR-2 POLYMORPHISM rs4696480 FOR THE DEVELOPMENT OF FOOD ALLERGY IN CHILDREN WITH ATOPIC DERMATITIS

Relevance. Food allergy is one of the most common chronic diseases in children. Toll-like receptors may be unique in the development of food allergies due to their expression by intestinal epithelial and dendritic cells.&#x0D; Objective. The aim of this study was to investigate the relationship between the rs4696480 polymorphism in TLR2 and the presence of food allergy in children with atopic dermatitis.&#x0D; Material and methods. The study included 103 patients with atopic dermatitis and 84 healthy children. Polymorphism genotyping was performed in the group of patients and the control group using real-time PCR. Food sensitization was determined by presence sIgE to food allergens by the immunochemiluminescent method using an ImmunoCAP 100 (Thermo Fisher Scientific Inc., Phadia, Sweden). The presence of food allergy was determined by a detailed clinical history and review of clinical records.&#x0D; Results. In the subgroup of children with food allergies, 9 children had the AA genotype, 7 patients had the heterozygous variant, and 3 children had the TT genotype. Among patients without food allergy, 20 patients had the AA genotype, 39 were heterozygotes, and 25 had the TT genotype. The OR assessment demonstrated that the AA genotype of the rs4696480 polymorphism is reliably associated with the development of food allergy in children with atopic dermatitis, OR=2,880 (1,0271-8,0757).&#x0D; Conclusion. The rs4696480 polymorphism in TLR2 gene is associated with the development of food allergy in Ukrainian children with atopic dermatitis.

Research Progress on the Correlation between the Intestinal Microbiota and Food Allergy

The increasing incidence of food allergy is becoming a substantial public health concern. Increasing evidence suggests that alterations in the composition of the intestinal microbiota play a part in the development of food allergy. Additionally, the application of probiotics to correct gut microbiota imbalances and regulate food allergy has become a research hotspot. However, the mechanism by which the gut microbiota regulates food allergy and the efficacy of probiotics are still in the preliminary exploration stage, and there are no clear and specific conclusions. The aim of this review is to provide information regarding the immune mechanism underlying food allergy, the correlation between the intestinal microbiota and food allergy, a detailed description of causation, and mechanisms by which the intestinal microbiota regulates food allergy. Subsequently, we highlight how probiotics modulate the gut microbiome–immune axis to alleviate food allergy. This study will contribute to the dovetailing of bacterial therapeutics with immune system in allergic individuals to prevent food allergy and ameliorate food allergy symptoms.

A pragmatic approach to infant feeding for food allergy prevention.

Early introduction of allergenic foods into an infant's diet is currently the most promising strategy to prevent food allergy, with infant guidelines around the world shifting from promoting avoidance to actively encourage the introduction of allergenic foods in the infant diet. Infant feeding guidelines vary according to regional public health priorities, and knowledge gaps remain, resulting in ongoing challenges for clinicians and families to translate guidelines into practical strategies for the introduction of complementary foods for food allergy prevention. Evidence from Australia demonstrates high community support and uptake of revised guidelines with most parents introducing allergenic foods in the first year of life, although this has not had the expected impact on substantially reducing food allergy prevalence. To uptake of guidelines from other countries is less clear, and several barriers have been noted in infant feeding RCTs, which may warrant intervention strategies. Further research is needed to understand additional strategies for food allergy prevention, particularly in infants who develop food allergy prior to when they are developmentally ready to commence solids. Several RCTs are underway investigating preventative strategies that target the window before allergen ingestion, such as vitamin D supplementation, emollient use, and immunizations that prime the immune response away from a Th2‐driven allergic phenotype. Further research is also needed to understand the role of the environment and the host environment in the development of tolerance to foods.

Problems of gut microbiota formation as a risk factor for the development of immunopathological diseases and opportunities for their prevention: A review

The formation of infant intestinal microbiota begins in the womb when there is a selective transport of certain bacteria from the intestine through the placenta and amniotic fluid which has been proved in experiments. The mode of delivery has a significant impact on the establishment of the intestinal biocenosis: babies born by caesarean section show a slower colonisation rate and a higher risk of developing food allergies later in life. Antibiotic therapy at an early age can permanently alter the composition of the intestinal microbiota and has a proven risk of developing a range of diseases, both immunopathological and metabolic. The type of feeding also has a significant impact. Exclusive breastfeeding from birth promotes the establishment of a bifidobacterial and bacteroide-dominated infant microbiota. Supplementation at birth and early transfer to complementary feeding contribute to microbiocenosis alteration and sensitisation to cow's milk protein. Probiotics due to their protective and immunomodulatory effects can improve the composition of the microbiota of breast milk and the baby's gut and their perinatal administration reduces the risk of food allergies and other diseases.

How primary care providers can help prevent food allergies

IgE-mediated food allergy rates have increased in recent decades, yet treatment options remain limited. Prevention strategies are thus essential. We will review recent research and consensus guidelines for food allergy prevention. Research has continued to support that early introduction of allergens via the gastrointestinal tract induces tolerance and prevents development of food allergy. In contrast, allergen sensitization may occur via transcutaneous allergen exposure. This is supported by research that shows a decreased risk of food allergy with aggressive treatment of atopic dermatitis. More recent research suggests that transcutaneous sensitization could also be facilitated by frequent emollient use in the absence of atopic dermatitis but definitive research is lacking. Murine models have shown a likely role of dysbiosis, or disruption of the body's normal healthy microbiome, in development of food allergy, yet human studies have yet to show a conclusive benefit of probiotics in the prevention of food allergy. Important approaches for food allergy prevention are: introduction of peanut and cooked egg at 4-6 months, early introduction of other allergenic foods, and early diagnosis and treatment of atopic dermatitis (because of a predisposition to food sensitization through the damaged skin barrier). More research is needed to clarify the role, if any, of emollient use and probiotics.

Dietary olive oil enhances the oral tolerance of the food allergen ovalbumin in mice by regulating intestinal microecological homeostasis.

Increasing evidence indicates that intestinal microecological imbalances are strongly associated with food allergen intolerance. This study investigated the effect of olive oil on food allergy susceptibility and intestinal microecology based on an ovalbumin (OVA)-sensitized mouse model. The results indicated that the allergic symptoms of sensitized mice were alleviated when they were supplemented with olive oil at 1-3g/kg per day for 7 weeks. Intestinal epithelium observation showed repaired ileum villi and upregulated tight junction (TJ) protein expression. Furthermore, the levels of the cytokines (e.g., IL-10) secreted by regulatory T cells were increased, whereas T helper 2 (Th2) cell-associated factors were decreased in lamina propria. Furthermore, 16S rRNA sequencing indicated reduced Burkholderiaceae and increased Clostridiaceae in the intestinal microflora. The results suggest that an olive oil-enriched diet may effectively prevent food allergies by regulating the intestinal microecological balance. PRACTICAL APPLICATIONS: Recent studies emphasized that intestinal ecological imbalance, including intestinal immunity and microflora structure, plays an important role in affecting the occurrence and development of food allergy. The present results implied that olive oil, one of the main components of the Mediterranean diet, can effectively ameliorate the symptoms of OVA-induced food allergy by regulating intestinal microecological homeostasis. Therefore, dietary supplementation with olive oil may be an effective strategy for preventing food allergies.

Analysis of the Serum Profile of Cytokines Involved in the T-Helper Cell Type 17 Immune Response Pathway in Atopic Children with Food Allergy.

The main risk factor for the development of food allergies (FAs) in children is atopic dermatitis (AD). AD is usually recognized as the Th1/Th2 paradigm of allergic disease. Recently, the Th1/Th2 paradigm in allergy and autoimmunity has been revised, including the role of the Th17 cell population and related cytokines. However, there are only a few studies that have found Th17 cytokine involvement in the allergic inflammatory response, especially with food allergens. This research aimed to analyze the serum profile of cytokines involved in the T-helper cell type 17 immune response pathway in young, atopic children with an IgE-mediated and delayed-type FA. The study involved 76 children (0–5 years old) with chronic AD. We used the Bio-Plex system to simultaneously determine the concentrations of 15 different cytokines in one experiment. In accordance with complete dermatological and allergological examination, including OFC testing and ALEX2 assays, participants were divided into 3 groups: IgE-mediated FA, delayed-type FA, and the control group. Data were analyzed using univariate statistical tests. In the IgE-mediated FA group, the circulating levels of tested cytokines had increased compared with those of other patients; however, a statistically significant difference was only obtained for IL-1beta (p < 0.05). According to the ROC curves, IL-1beta may be considered an effective predictor of IgE-mediated FA in AD children (p < 0.05; AUC = 0.67). In the delayed-type FA group, the concentration of most cytokines had slightly decreased compared to the control group. The obtained results suggest that FA influences the Th17-related cytokine profile in the serum of AD children. More advanced studies are needed to confirm the involvement of Th17 cytokines in the allergic inflammatory response and to prove their usefulness in clinical practice.

The Case for Prompt Salvage Infant Peanut Oral Immunotherapy Following Failed Primary Prevention

Recent guideline recommendations have shifted from recommending prolonged avoidance of allergenic foods in the first 3 years of life to a primary prevention approach involving the deliberate early introduction to infants at risk of developing food allergy. Despite this, some infants, especially those with severe eczema who are at highest risk for developing peanut allergy, fail to receive the preventative benefits of early peanut introduction due to hesitancy and other factors. Difficulty adhering to regular ingestion after introduction further reduces the effectiveness of primary prevention. As emerging real-world evidence has demonstrated that performing peanut oral immunotherapy (OIT) among infants is effective and safe, peanut OIT could be a treatment option for infants with peanut allergy. This review discusses the benefits, risks, and barriers to offering peanut OIT to infants who fail primary prevention strategies. We propose the novel concept that infants with peanut allergy be offered peanut OIT as soon as possible after failed peanut introduction through a shared decision-making process with the family, where there is a preference for active management rather than avoidance.

Early Introduction of Allergenic Foods and the Prevention of Food Allergy.

The increasing prevalence of food allergies is a growing public health problem. For children considered high risk of developing food allergy (particularly due to the presence of other food allergies or severe eczema), the evidence for the early introduction of allergenic foods, and in particular peanut and egg, is robust. In such cases, the consensus is clear that not only should such foods not be delayed, but that they should be introduced at approximately 4 to 6 months of age in order to minimize the risk of food allergy development. The early introduction of allergenic foods appears to be an effective strategy for minimizing the public health burden of food allergy, though further studies on the generalizability of this approach in low-risk populations is needed.

Filaggrin loss-of-function mutations are associated with persistence of egg and milk allergy

A genetic defect in the epidermal barrier protein filaggrin (FLG) plays a major role in the etiology of eczema and associated allergic airways diseases. However, it is still controversial to what extend loss-of-function (LOF) mutations in FLG contribute to the development and persistence of food allergies. This study tested association of FLG LOF mutations with allergic reactions to diverse foods and investigated their potential effect on the persistence of early food allergies. This study recruited 890 children with challenge-proven food allergy for the German Genetics of Food Allergy Study (GOFA). Longitudinal data were available for 684 children. All children were clinically characterized, including their allergic responses to specific foods, and genotyped for the 4 most common LOF mutations in FLG; R501X, 2282del4, R2447X, and S3247X. Associations between FLG mutations and food allergies were analyzed by logistic regression using the German Multicenter Allergy Study cohort as the control population. FLG mutations were associated with allergies to diverse foods including hen's egg (HE), cow's milk (CM), peanut, hazelnut, fish, soy, cashew, walnut, and sesame with similar risk estimates. Effects remained significant after adjusting for the eczema status. Interestingly, FLG mutations increased the risk of a persistent course of HE and CM allergy. Using the gold standard for food allergy diagnosis, this study demonstrates that FLG LOF mutations confer a risk of any food allergy independent of eczema. These mutations predispose to the persistence of HE and CM allergy and should be considered in the assessment of tolerance development.

Intestinal Uptake and Tolerance to Food Antigens.

Food allergy is a growing concern due to its increasing world-wide incidence. Strict avoidance of allergens is a passive treatment strategy. Since the mechanisms responsible for the occurrence and development of food allergy have not yet been fully elucidated, effective individualized treatment options are lacking. In this review, we summarize the pathways through which food antigens enter the intestine and review the proposed mechanisms describing how the intestine acquires and tolerates food antigens. When oral tolerance is not established, food allergy occurs. In addition, we also discuss the contribution of commensal bacteria of the gut in shaping tolerance to food antigens in the intestinal tract. Finally, we propose that elucidating the mechanisms of intestinal uptake and tolerance of food antigens will provide additional clues for potential treatment options for food allergy.

Prevalence and risk factors for food allergy in children: a review of epidemiological studies

BACKGROUND: Food allergy is an actual problem in pediatric practice. In recent decades, there has been an increase in the prevalence of food allergies, as well as an increase in the number of severe cases.&#x0D; AIM: To assess the prevalence of food allergy and the role of hereditary and environmental factors in food allergy development in children according to epidemiological cohorts and cross-sectional studies.&#x0D; MATERIALS AND METHODS: A systematic review of epidemiological cohorts and cross-sectional studies published between January 1, 2000 and December 31, 2021, was conducted This review investigated the developmental factors and prevalence of food allergy.&#x0D; RESULTS: This review made it possible to generalize and systematize the accumulated worldwide scientific data on food allergy. An analysis of epidemiological studies revealed a significant prevalence of food allergy, which reflected the natural course of the disease; the highest rates were found among young children, and by school age, the prevalence of symptoms and confirmed food allergy is gradually decreasing. Based on epidemiological data, the main risk factors for food allergy are hereditary predisposition and environmental factors that modify the microbial environment.&#x0D; CONCLUSION: It is necessary to further study the genetic markers of food allergy, as well as the role of microbiotic factors in the implementation of hereditary predisposition to allergic diseases.

Mycophenolate mofetil use is associated with reduced incidence of food allergy in liver transplanted children.

The incidence of food allergy in children following liver transplantation is high and the pathogenesis is still not known. We aimed to identify risk factors for development of food allergies in liver transplant children. 107 children and adolescents who underwent liver transplantation from 1999 to 2019 were included. Data were retrospectively collected from medical records included total and specific IgE, eosinophil cationic protein and eosinophil count 12 months after transplantation and at yearly follow up (median follow-up). 24/107 (22%) patients reported clinical food reactions. Median time from transplantation to debut of food allergy was 1.6 (IQR 0.6-3.3) years. Mycophenolate mofetil (MMF) was discontinued in 24/78 patients (31%) due to side effects. Children treated with MMF in addition to tacrolimus one year after transplantation reported less food allergy (12.5% vs. 37.8%, p=0.003) and sensitization to food allergens one year after transplantation (8.9% vs. 17.8%, p=0.02) than those not receiving MMF. Tacrolimus trough levels did not differ between the patients treated with MMF and those who were not. Treatment with MMF two years after transplantation was associated with less food allergy (p=0.001) and food sensitization (p=0.002), also when adjusted for age at transplantation (p=0.006 and p=0.03, respectively) or for use of basilixmab (p=0.015 and p=0.018, respectively). Basiliximab was also associated with less food allergy. Use of MMF one and two years after transplantation was associated with less food allergy and sensitization against food allergens. The effect of MMF was not due to reduced trough levels of of tacrolimus. An infographic is available for this article at: https://links.lww.com/MPG/C821.

Epigenetic/genetic variations in CG-rich elements of immune-related genes contribute to food allergy development during childhood.

Genetic areas of FOXP3 TSDR, human leukocyte antigen-G (HLA-G) upstream of CpG island 96, CpG41 and CpG73 islands of the HLA-DRB1 and HLA-DQB1 genes respectively, previously documented to display immune-modulatory properties, were subjected to epigenetic/genetic analysis to assess their influence in IgE-mediated food allergy (FA) development in children. Sixty-four orally challenged and IgE-tested food allergic subjects together with 44 controls were recruited. Targeted pyrosequencing analysis to detect DNA methylation status and genetic variations was utilized and experimental results obtained were analyzed by a statistical software platform and correlated to clinical data. Also, transcription factor (TF) binding sites in study areas were unmasked by the JASPAR prediction database. Parents' smoking was significantly correlated with aberrant methylation patterns, regardless of food allergic or control status. HLA-G promoter region showed a trend for hypomethylation in food allergic subjects, with one of the CG sites displaying significantly decreased methylation values. Rs1233333, residing within the HLA-G promoter region preserved a protective role toward DNA methylation. Variable methylation patterns were recorded for CpG41 of the HLA-DRB1 gene and hypermethylation of the region was significantly correlated with the presence of single nucleotide polymorphisms (SNPs). TFs' recognition sites, located in studied genetic areas and exerting pivotal regulatory biological roles, are potentially affected by divergent DNA methylation status. We propose that HLA-G expression is triggered by food-derived allergens, providing a TregFoxP3-/HLA-G+ subpopulation generation to promote direct immune tolerance. Furthermore, clear evidence is provided for the underlying co-operation of genetic polymorphisms with epigenetic events, mainly at the CpG41 island of the HLA-DRB1 gene, which needs an extended investigation and elucidation.

Development of allergen-specific IgE in a food-allergy model requires precisely timed B cell stimulation and is inhibited by Fgl2.

SUMMARYImmunoglobulin E (IgE) responses are a central feature of allergic disease. Using a well-established food-allergy model in mice, we show that two sensitizations with cognate B cell antigen (Ag) and adjuvant 7 days apart promotes optimal development of IgE+ germinal center (GC) B cells and high-affinity IgE production. Intervals of 3 or 14 days between Ag sensitizations lead to loss of IgE+ GC B cells and an undetectable IgE response. The immunosuppressive factors Fgl2 and CD39 are down-regulated in T follicular helper (TFH) cells under optimal IgE-sensitization conditions. Deletion of Fgl2 in TFH and T follicular regulatory (TFR) cells, but not from TFR cells alone, increase Ag-specific IgE levels and IgE-mediated anaphylactic responses. Overall, we find that Ag-specific IgE responses require precisely timed stimulation of IgE+ GC B cells by Ag. Furthermore, we show that Fgl2 is expressed by TFH cells and represses IgE. This work has implications for the development and treatment of food allergies.