Mechanisms of adverse gastrointestinal events during oral immunotherapy

口服免疫治疗期间胃肠道不良事件的机制

• 批准号: 10365516
• 负责人: Benjamin L. Wright
• 金额: $ 18.99万
• 依托单位: MAYO CLINIC ARIZONA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-21 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10365516
• 关键词: Address; Adverse effects; Allergic; Allergic Disease; Allergy to peanuts; Antibodies; Applications Grants; Arizona; Asthma; Atopic Dermatitis; Award; Basal Cell Hyperplasia; Basic Science; Bioethics; Biological Markers; Biology; Biometry; Blood; CCL26 gene; Caring; Cell Adhesion Molecules; Cellular Immunology; Characteristics; Chemotactic Factors; Chronic; Clinic; Clinical; Clinical Immunology; Clinical Research; Clinical Trials; Collaborations; Data; Development; Diagnosis; Disease; Edema; Endoscopic Biopsy; Environment; Eosinophilia; Eosinophilic Esophagitis; Eosinophilic Gastrointestinal Disease; Epithelial; Esophagus; Event; Exposure to; Extracellular Space; FDA approved; Food; Food Hypersensitivity; Functional disorder; Funding; Goals; Health; Hour; Hypersensitivity; Iatrogenesis; IgE; Immune Tolerance; Immune response; Immunity; Immunologics; Immunology; Individual; Interleukin-13; Interleukin-4; International; Internships; Knowledge; Lead; Life; Mediating; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methods; Milk; Milk Hypersensitivity; Monitor; Nose; Outcome; Parents; Pathogenesis; Patient Care; Patients; Peripheral Blood Mononuclear Cell; Placebos; Production; Proteomics; Randomized; Request for Applications; Research; Research Design; Research Personnel; Research Proposals; Research Technics; Research Training; Risk; Safety; Sampling; Signal Transduction; Symptoms; Testing; Th2 Cells; Tissues; Training; Training Support; Translating; Translational Research; United States National Institutes of Health; Universities; Vascular Cell Adhesion Molecule-1; career; career development; clinical practice; cytokine; desensitization; design; double-blind placebo controlled trial; eosinophil; eosinophilic inflammation; experience; food antigen; gastrointestinal; gastrointestinal symptom; immunotherapy clinical trials; improved; inflammatory marker; insight; minimally invasive; novel; oral immunotherapy; patient oriented research; peripheral blood; placebo controlled trial; polyposis; prevent; professor; programs; prospective; response; side effect; skills; treatment strategy

ABSTRACT This K23 award application requests support for the career development of Dr. Benjamin Wright, Assistant Professor in the Division of Allergy, Asthma and Clinical Immunology at Mayo Clinic Arizona. The candidate’s overall goal is to become an independent, clinician-investigator and improve the health of individuals with eosinophilic esophagitis (EoE) and food allergy through patient-oriented research. This award will provide the training and support needed to accomplish this goal. Specifically, this proposal will enable Dr. Wright to accomplish the following short-term career goals: (1) acquire training in methods and design of clinical studies and trials in food allergy; (2) develop skills in basic/translational research techniques; (3) develop professional skills necessary to lead a translational research team; and (4) gather preliminary data and biospecimens for a subsequent R01 application and establish an independent research program in food allergy and eosinophilic gastrointestinal disorders. Oral immunotherapy (OIT) is an emerging treatment for food allergy. Although most patients can be successfully desensitized with OIT, many develop gastrointestinal side effects including EoE. EoE is a chronic allergic condition associated with severe esophageal dysfunction. The specific goals of the research proposal are to examine the mechanisms underlying the gastrointestinal side effects of OIT and to develop a novel treatment strategy to prevent them. To accomplish this, we will perform a sub-study of a placebo-controlled trial in patients with milk allergy treated with milk OIT with or without dupilumab. During the trial, we will serially monitor eosinophilic inflammation, markers of esophageal barrier dysfunction, and immune responses in peripheral blood and in the esophagus. To support Dr. Wright’s career development, he will acquire skills in cellular immunology and complete a basic science internship focusing on cutting-edge proteomic analysis of clinical samples. In addition, he will complete formal didactic coursework in clinical research study design, biostatistics, and bioethics. Dr. Wright has assembled a mentoring committee comprised of international experts in food allergy, EoE, proteomics, eosinophil biology, and type 2 immunity uniquely suited to address the hypotheses set forth in this proposal and guide Dr. Wright’s career development. This proposal combines the strength of the research environment at Mayo Clinic and an ongoing collaboration with Stanford University that provides an ideal setting to pursue the aforementioned training and research goals. At the conclusion of this program, Dr. Wright will have the skillset and experience required to transition to independence and lead a translational research team. Successful completion of this project will likely provide a major and sustained impact on the care of patients with food allergy by providing critical insights into the pathogenesis of food allergy and EoE.

摘要