Food allergy is a growing problem with limited treatment options. It is important to understand the mechanisms of food tolerance and allergy to promote the development of directed therapies. Dendritic cells are specialized antigen presenting cells that prime adaptive immune responses, such as those involved in the development of oral tolerance and food allergies. The dendritic cell subsets in the gut and skin are defined by their surface markers and function. The default response to an ingested innocuous antigen is oral tolerance, which requires either gut dendritic cells or a subset of newly identified RORγt+ antigen presenting cells to induce the development of gut peripheral T regulatory cells. However, dendritic cells in the skin, gut, and lung can also promote allergic sensitization when they are activated under certain inflammatory conditions, such as with alarmin release or gut dysbiosis. Dendritic cells also play a role in the responses to the various modalities of food immunotherapy. Langerhans cells in the skin appear to be necessary for the response to epicutaneous immunotherapy. It will be important to determine which real-world stimuli activate the dendritic cells that prime allergic sensitization and discover methods to selectively initiate a tolerogenic program in antigen presenting cells.

BACKGROUND: Oral immunotherapy (OIT) has emerged as the most popular therapy for food allergy. However, data on the long-term adherence and efficacy of this approach are sparse.
OBJECTIVE: We aimed to assess the long-term adherence rates to OIT protocol and the associated risk of allergic reactions.
METHODS: Patients who completed milk OIT and reached a maintenance dose of 200 ml of milk were surveyed biannually on their dairy consumption and occurrence of allergic reactions. A survival analysis was performed to evaluate the association between the risk of reaction and adherence to OIT maintenance protocol.
RESULTS: The cohort consisted of 50 patients. Only 56% of the cohort adhered to protocol, which consisted of ingesting a minimum of 200 ml of milk at least 3 times per week. Adherent patients had a significantly reduced risk of allergic reactions, as well as a reduced incidence of anaphylaxis, healthcare/ER visits, and epinephrine/antihistamine administration.
CONCLUSIONS: The findings demonstrate the importance of consistent maintenance dose consumption in the management of food allergies, with regular milk consumption contributing to the maintenance of unresponsiveness and decreased risk of allergic symptoms.

CONCLUSIONS: Low-dose wheat oral immunotherapy with 53 mg of wheat protein for 6 years increased children\'s short-term unresponsiveness to 400-600 mg and decreased the adverse reaction over time. Low-dose oral immunotherapy can be safe and effective for children with wheat-induced anaphylaxis.

Food allergy, a group of adverse immune responses to normally innocuous food protein antigens, is an increasingly prevalent public health issue. The most common form is IgE-mediated food allergy in which food antigen-induced crosslinking of the high-affinity IgE-receptor, FcεRI, on the surface of mast cells triggers the release of inflammatory mediators that contribute to a wide range of clinical manifestations, including systemic anaphylaxis. Mast cells also play a critical function in adaptive immunity to foods, acting as adjuvants for food-antigen driven Th2 cell responses. While the diagnosis and treatment of food allergy has improved in recent years, no curative treatments are currently available. However, there is emerging evidence to suggest that both allergen-specific IgA and IgG antibodies can counter the activating effects of IgE antibodies on mast cells. Most notably, both antigen-specific IgA and IgG antibodies are induced in the course of oral immunotherapy. In this review, we highlight the role of mast cells in food allergy, both as inducers of immediate hypersensitivity reactions and as adjuvants for type 2 adaptive immune responses. Furthermore, we summarize current understanding of the immunomodulatory effects of antigen-specific IgA and IgG antibodies on IgE-induced mast cell activation and effector function. A more comprehensive understanding of the regulatory role of IgA and IgG in food allergy may provide insights into physiologic regulation of immune responses to ingested antigens and could seed novel strategies to treat allergic disease.

BACKGROUND: Cow\'s milk and egg allergy affect approximately 1.9% and 0.9% of children, respectively. Dietary advancement therapies (DAT), including milk (ML) and egg (EL) ladders, baked milk (BM-OIT) and baked egg (BE-OIT) oral immunotherapy are potential therapeutic options for these patients.
OBJECTIVE: To perform systematic review and meta-analysis of the safety and efficacy of DAT in children with IgE-mediated milk or egg allergy.
METHODS: A systematic literature review was conducted, exploring 22 potential outcomes, with meta-analysis performed where >3 studies reported data. The GRADE approach was used to determine the certainty of evidence for each outcome, and the Johanna Briggs Institute tools for determining risk of bias.
RESULTS: Twenty-nine studies met inclusion criteria among 9946 titles screened. Tolerance occurred in 69% of EL, 58% of ML, 49% of BE-OIT and 29% of BM-OIT patients. All-severity allergic reactions occurred in 21% of EL, 25% of ML, 20% of BE-OIT and 61% of BM-OIT patients, with epinephrine use in 3% of EL, 2% of ML, and 9% of BM-OIT patients. At-home reactions occurred in 19% of BE-OIT and 10% of BM-OIT patients. Discontinuation occurred in 14% of EL, 17% of ML, 17% of BE-OIT and 20% of BM-OIT patients. Mean time to BE egg and BE-OIT tolerance was 13.25 months (4 studies) and 19.1 months (3 studies). Certainty of evidence was very low, and risk of bias high. Study heterogeneity was high, attributable to multiple factors.
CONCLUSIONS: There is very low certainty of evidence supporting DAT safety and efficacy. We cannot conclude DAT accelerates tolerance development.

Atopic dermatitis (AD) is one of the main risk factors for infants in the development of food allergy. Oral immunotherapy (OIT) in early childhood has been found to be highly effective and safe in preschoolers with and without AD, especially in young infants. Delays in initiation of OIT in infants and children due to uncontrolled AD risk expansion of the number of foods children develop allergy to through unnecessary avoidance of multiple foods. Parents and caregivers may attribute eczema flares to OIT doses, which physicians usually ascribe to non-food triggers such as weather changes, psychological stress, and infection. There is a lack of published literature confirming OIT as a trigger of AD flares, and the degree to which OIT may be associated with AD flares needs to be further studied. We describe 8 case scenarios with varying degrees of AD flare before and during OIT. We propose management algorithms for children with preexisting concurrent AD and food allergy who are being considered for starting OIT and children with AD flares during OIT. Optimizing AD control strategies and providing adequate AD care education before starting OIT can reduce confusion for both parents and allergists if rashes arise during OIT, thus improving adherence to OIT.

The OIT-BRAVE questionnaire was developed to serve as a clinical screening tool to identify patients who may be experiencing adverse effects with oral immunotherapy.

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Oral immunotherapy (OIT) is an alternative treatment of IgE-mediated food allergy that has been shown to increase tolerance threshold to many of the top food allergens, although this effect may be dependent on age, dose, frequency, and duration. OIT has been shown to be effective and safe in infants, and early initiation can improve rates of desensitization even for those foods whose natural history favors loss of allergy. Studies looking at protocol modification to improve OIT success are ongoing as is the evaluation of clinical tools to help monitor OIT effects.

Oral immunotherapy with apple induces tolerance for an entire apple (128 g) in patients with pollen food allergy syndrome who previously tolerated a median amount of 4 g of apple.