Understanding the Mechanism of Mucosal Immunotherapy

了解粘膜免疫治疗的机制

• 批准号: 8692631
• 负责人: A. Wesley Burks
• 金额: $ 37.28万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8692631
• 关键词: Adult; Allergen Immunotherapy; Allergens; Allergic; Allergy to peanuts; Anaphylaxis; Antigens; Apoptosis; B-Lymphocytes; Basophils; Blinded; CD4 Positive T Lymphocytes; Cells; Child; Clinical; Complex; Data; Development; Food; Food Hypersensitivity; Frequencies; Goals; Human; Hypersensitivity; IL2RA gene; IgE; IgE Receptors; IgG4; Immune response; Immunoglobulin A; Immunotherapy; Life; Link; Mediating; Membrane Microdomains; Patients; Peanuts - dietary; Phenotype; Reaction; Regulatory T-Lymphocyte; Risk; Serum; Signal Pathway; Signal Transduction; T cell response; T-Lymphocyte; Time; United States; base; cytokine; desensitization; in vitro Model; mast cell; oral immunotherapy; oral tolerance; response; skin prick test; uptake; Adult; Allergen Immunotherapy; Allergens; Allergic; Allergy to peanuts; Anaphylaxis; Antigens; Apoptosis; B-Lymphocytes; Basophils; Blinded; CD4 Positive T Lymphocytes; Cells; Child; Clinical; Complex; Data; Development; Food; Food Hypersensitivity; Frequencies; Goals; Human; Hypersensitivity; IL2RA gene; IgE; IgE Receptors; IgG4; Immune response; Immunoglobulin A; Immunotherapy; Life; Link; Mediating; Membrane Microdomains; Patients; Peanuts - dietary; Phenotype; Reaction; Regulatory T-Lymphocyte; Risk; Serum; Signal Pathway; Signal Transduction; T cell response; T-Lymphocyte; Time; United States; base; cytokine; desensitization; in vitro Model; mast cell; oral immunotherapy; oral tolerance; response; skin prick test; uptake

DESCRIPTION (provided by applicant): Food allergy, an aberration of oral tolerance, occurs in 6% of children and 3.5% of adults in the United States. Peanut allergy is one of the most common food allergies; most children develop this allergy early in life, do not outgrow it and are at risk for severe and life-ending anaphylactic reactions. Currently there is not a proactive treatment for peanut allergy but we along with others are developing specific types of immunotherapy that will cause these patients to be no longer allergic to peanuts. The significance of this proposal is based on our landmark studies that have examined the effects of peanut oral immunotherapy (OIT) showing a substantial increase in the amount of peanut that a peanut allergic patient can ingest while on therapy (desensitization) and in some cases causing long-term clinical tolerance when the therapy is discontinued. We have identified initial changes in basophil/mast cell reactivity, antigen-specific T cell responses and systemic humoral immune responses in these subjects. Our hypothesis is that peanut OIT will alter the early signaling pathways of basophils/mast cells causing clinical desensitization and then clinical tolerance will develop because of the interrelated changes in allergen-specific T- and B-cells. The long-term goal of this proposal is to better understand the mechanism of the development of oral tolerance to foods in young children treated with allergen immunotherapy. To accomplish this goal our specific aims are the following: Aim 1: Determine the mechanism(s) by which OIT induces hyporesponsiveness in basophils/mast cells in peanut allergic subjects on peanut OIT, Aim 2: Determine the peanut allergen-specific CD4+ T cell frequencies and phenotypes, as well as the suppressive function of Treg cells, that are associated with the development of clinical tolerance to peanuts, Aim 3: Determine the effect of peanut-specific mucosal and systemic humoral immune responses in OIT on clinical tolerance. The studies will help us identify the mechanism and durability of the desensitized state and then the development of tolerance to foods after OIT. A treatment for peanut allergy is critically needed, the completion of these studies will provide a strong scientific basis for the development of OIT and other types of therapy that hope to produce long-term clinical tolerance to peanuts and other foods.

描述（由申请人提供）：食物过敏是口服耐受的畸变，发生在美国6％的儿童和3.5％的成年人中。花生过敏是最常见的食物过敏之一。大多数儿童在生命的早期就会发展出这种过敏，不要超越它，并且面临严重和寿命的过敏反应的风险。目前，没有积极的花生过敏治疗方法，但我们与其他人一起开发了特定类型的免疫疗法，这将导致这些患者不再对花生过敏。该提案的重要性是基于我们的地标研究，该研究检查了花生口服免疫疗法（OIT）的影响，表明花生过敏患者在治疗时可能会摄入的花生量大幅增加（脱敏），在某些情况下会导致长期临床耐受性，而治疗则在治疗中均可摄入。我们已经确定了这些受试者中嗜碱性/肥大细胞反应性，抗原特异性T细胞反应和全身体液免疫反应的初始变化。我们的假设是，由于过敏原特异性T和B细胞的相互关联变化，花生OIT将改变引起临床脱敏的嗜碱性/肥大细胞的早期信号传导途径，然后会发展临床耐受性。该提案的长期目标是更好地了解接受过敏原免疫疗法治疗的幼儿口服耐受性的机制。 To accomplish this goal our specific aims are the following: Aim 1: Determine the mechanism(s) by which OIT induces hyporesponsiveness in basophils/mast cells in peanut allergic subjects on peanut OIT, Aim 2: Determine the peanut allergen-specific CD4+ T cell frequencies and phenotypes, as well as the suppressive function of Treg cells, that are associated with the development of clinical tolerance to peanuts,目标3：确定OIT中花生特异性粘膜和全身性体液免疫反应对临床耐受性的影响。这些研究将有助于我们确定脱敏状态的机制和耐用性，然后确定OIT之后对食物的耐受性的发展。需要对花生过敏的治疗方法进行迫切需要，这些研究的完成将为开发OIT和其他类型的疗法提供强大的科学依据，以期为花生和其他食物产生长期的临床耐受性。