Efficacy and safety of oral immunotherapy in children aged 1-3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study.

Background: For young children with peanut allergy, dietary avoidance is the current standard of care. We aimed to assess whether peanut oral immunotherapy can induce desensitisation (an increased allergic reaction threshold while on therapy) or remission (a state of non-responsiveness after discontinuation of immunotherapy) in this population.

Methods: We did a randomised, double-blind, placebo-controlled study in five US academic medical centres.

Tick salivary gland extract induces alpha-gal syndrome in alpha-gal deficient mice.

Introduction: Alpha-gal syndrome (AGS) is characterized by delayed hypersensitivity to non-primate mammalian meat in people having specific immunoglobulin E (sIgE) to the oligosaccharide galactose-alpha-1,3-galactose. AGS has been linked to tick bites from Amblyomma americanum (Aa) in the U.S.

Hypoallergenic Proteins for the Treatment of Food Allergy.

Purpose Of Review: Food allergy is a growing health problem worldwide that impacts millions of individuals. Current treatment options are limited and strict dietary avoidance remains the standard of care. Immunotherapy using whole, native allergens is under active clinical investigation but harbors the risk of severe side effects including anaphylaxis.

Antigenic Liposomes for Generation of Disease-specific Antibodies.

Antibody responses provide critical protective immunity to a wide array of pathogens. There remains a high interest in generating robust antibodies for vaccination as well as understand how pathogenic antibody responses develop in allergies and autoimmune disease. Generating robust antigen-specific antibody responses is not always trivial.

Characterization of the B-cell receptor repertoires in peanut allergic subjects undergoing oral immunotherapy.

B-cell receptors (BCRs) play a critical role in adaptive immunity as they generate highly diverse immunoglobulin repertoires to recognize a wide variety of antigens. To better understand immune responses, it is critically important to establish a quantitative and rapid method to analyze BCR repertoire comprehensively. Here, we developed "Bcrip", a novel approach to characterize BCR repertoire by sequencing millions of BCR cDNA using next-generation sequencer.

Mast cell desensitization inhibits calcium flux and aberrantly remodels actin.

Rush desensitization (DS) is a widely used and effective clinical strategy for the rapid inhibition of IgE-mediated anaphylactic responses. However, the cellular targets and underlying mechanisms behind this process remain unclear. Recent studies have implicated mast cells (MCs) as the primary target cells for DS.

Peanut Allergy: New Developments and Clinical Implications.

Food allergies have increased in prevalence over the past 20 years, now becoming an important public health concern. Although there are no therapies currently available for routine clinical care, recent reports have indicated that immunotherapies targeting the mucosal immune system may be effective. Oral immunotherapy is conducted by administering small, increasing amounts of food allergen; it has shown promise for desensitizing individuals with peanut, egg, or milk allergies.

Diagnosis, management, and investigational therapies for food allergies.

Food allergies have increased in prevalence over the past 20 years, now becoming an important public health concern. Although there are no therapies currently available for routine clinical care, recent reports have indicated that immunotherapies targeting the mucosal immune system may be effective. Oral immunotherapy is conducted by administering small, increasing amounts of food allergen; it has shown promise for desensitizing individuals with peanut, egg, or milk allergies.

Novel strategy to create hypoallergenic peanut protein-polyphenol edible matrices for oral immunotherapy.

Peanut allergy is an IgE-mediated hypersensitivity. Upon peanut consumption by an allergic individual, epitopes on peanut proteins bind and cross-link peanut-specific IgE on mast cell and basophil surfaces triggering the cells to release inflammatory mediators responsible for allergic reactions. Polyphenolic phytochemicals have high affinity to bind proteins and form soluble and insoluble complexes with unique functionality.

Type B CpG oligodeoxynucleotides induce Th1 responses to peanut antigens: modulation of sensitization and utility in a truncated immunotherapy regimen in mice.

Scope: Peanut allergy stems from a Th2-biased immune response to peanut allergens leading to IgE production and allergic reactions upon ingestion.

Methods And Results: A model of peanut allergy in C3H/HeJ mice was used to assess whether type A, B, or C CpG oligodeoxynucleotide (ODN) molecules would be effective in: (i) a prophylactic approach to prevent peanut allergy when administered simultaneously with a Th2-skewing adjuvant, and (ii) a therapeutic model to allow for shortened immunotherapy. Type B ODNs were extremely effective in inhibiting anaphylaxis in the sensitization protocol as evidenced by differences in symptom scores, body temperature, and mouse mast cell protease 1 release compared to sham treatment.

Oral immunotherapy for food allergy: clinical and preclinical studies.

Food allergies affect approximately 5% of the U.S. population and have increased in the last decade.

Pepsinized cashew proteins are hypoallergenic and immunogenic and provide effective immunotherapy in mice with cashew allergy.

Background: IgE-mediated allergic reactions to cashews and other nuts can trigger life-threatening anaphylaxis. Proactive therapies to decrease reaction severity do not exist.

Objectives: We aimed to determine the efficacy of pepsin-digested cashew proteins used as immunotherapy in a murine model of cashew allergy.

Diacylglycerol kinase ζ deficiency in a non-CD4(+) T-cell compartment leads to increased peanut hypersensitivity.

Peanut sensitization in diacylglycerol kinase zeta (DGKζ) deficient mice led to elevated peanut-IgE levels and severe anaphylaxis. DGKζ deficient CD4T cells did not account for the phenotype. Future studies will determine which immune lineage caused increased food hypersensitivity.

A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response.

Background: 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.

Objective: To investigate the safety and effectiveness of OIT for peanut allergy in a double-blind, placebo-controlled study.

Pioneering immunotherapy for food allergy: clinical outcomes and modulation of the immune response.

There is no approved therapy for food allergies, which affect 12 million people in the United States and millions more worldwide. In the last few years, our research team at Duke has begun to develop protocols to treat peanut and other food allergies. Two distinct therapies are being developed.

Single-tree nut immunotherapy attenuates allergic reactions in mice with hypersensitivity to multiple tree nuts.

Background: Allergic reactions to tree nuts are often severe and are outgrown in less than 10% of diagnosed patients.

Objectives: To determine whether treatment of underlying tree nut sensitization will prevent allergic reactions to cross-reacting tree nuts and to determine the effects of single-tree nut immunotherapy on true multi-tree nut sensitization.

Methods: Cross-reactivity model: Cashew-sensitized mice underwent immunotherapy with cashew and were subsequently challenged with cashew and pistachio.

Clinical efficacy and immune regulation with peanut oral immunotherapy.

Background: Oral immunotherapy (OIT) has been thought to induce clinical desensitization to allergenic foods, but trials coupling the clinical response and immunologic effects of peanut OIT have not been reported.

Objective: The study objective was to investigate the clinical efficacy and immunologic changes associated with OIT.

Methods: Children with peanut allergy underwent an OIT protocol including initial day escalation, buildup, and maintenance phases, and then oral food challenge.

Food allergies and hypersensitivity: a review of pharmacotherapy and therapeutic strategies.

Background: Food allergy is a major cause of life-threatening hypersensitivity reactions. Food-induced anaphylaxis is the most common reason for someone to present to the emergency department for an anaphylactic reaction. At present, the avoidance of the allergenic food is the only method of preventing further reactions for allergic patients.