Interactions of lgC4 & lgE anti-Dsg1 Autoantibodies in Endemic Pemphigus Foliaceu

lgC4 的相互作用

• 批准号: 8693332
• 负责人: Ye Qian
• 金额: $ 3.98万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-06 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8693332
• 关键词: Advisory Committees; Age; Allergens; Amerindian; Antibodies; Antigens; Area; Autoantibodies; Autoimmune Process; Autoimmune Responses; Autoimmunity; Basophils; Biology; Biometry; Brazil; Bulla; Cities; Clinical; Cutaneous; Detection; Development; Development Plans; Disease; Epitope Mapping; Etiology; Evaluation; Generations; Genes; Genetic; Grant; Histamine Release; Human; Hybridomas; Hypersensitivity; IgE; IgE Receptors; Immunoglobulin G; In Vitro; In complete remission; Individual; Laboratories; Leishmaniasis; Life; Light; Link; Mentored Research Scientist Development Award; Mentors; Methods; Monoclonal Antibodies; Mus; Nature; Neonatal; Onchocerciasis; Passive Transfer of Immunity; Pathogenesis; Pathogenicity; Patients; Pattern; Pemphigus; Pemphigus Vulgaris; Phage Display; Play; Population; Prevalence; Principal Investigator; Research; Research Personnel; Reservations; Role; Rural; Secure; Serological; Serum; Somatic Mutation; Staging; Technology; Testing; Training; Training Programs; Transgenic Organisms; Work; anti-IgE; anti-IgG; anti-IgM; base; career; career development; cohort; cytokine; design; desmoglein 1; environmental allergen; follow-up; in vivo; member; mouse model; neonate; pathogen; pre-clinical; response; skin disorder

DESCRIPTION (provided by applicant): The P.I. has recently entered the research field of cutaneous autoimmunity. His career development plan is designed to secure advanced training in this field and prepare him to become an independent investigator under the guidance of his mentor, Dr. L.A. Diaz, who is internationally recognized as a leader in the field of skin diseases. To enhance the training, the program has enlisted the expertise of an advisory committee that consists of established investigators with expertise in the field of cutaneous biology, autoimmunity and allergy, and biostatistics for the scientific and career advice. The P.I. have been studying the mechanism of the development of auto antibodies in endemic [Fogo Selvagem (FS)] and non-endemic pemphigus foliaceus (PF) and pemphigus vulgaris (PV). He is focusing on the initiation and development of pathogenic anti- desmoglein 1 (Dsg1) auto antibodies that are found in these patients. This grant explores the interaction of self-reactive IgE antibodies and pathogenic lgG4 auto antibodies in FS. Recent work in our laboratory demonstrated that FS patients have significantly higher levels of anti-Dsgl IgE antibodies compared to healthy controls. We hypothesize that the lgG4 and IgE anti-Dsgl autoantibody responses in FS are triggered by the same environmental antigen ("allergen"). The candidate's immediate research plan is to provide evidence that the IgE and lgG4 autoantibody response in FS is relevant to the pathogenesis of the disease. Aim 1 will focus on the interactions of IgE and lgG4 anti-Dsgl response in FS patients and healthy individuals from endemic areas of FS. In Aim 2, we will generate anti-Dsgl IgE monoclonal antibodies to study their V gene usage, and analyze whether there is any genetic relationship between anti-Dsgl lgG4 and IgE auto antibodies in the same FS patients through their "clonal signature". In Aim 3, we will determine the pathogen city of anti-Dsgl IgE antibodies by the passive transfer mouse model. The successful conclusion of this project will shed light on our understanding of the mechanism of etiology and pathogenesis of FS, as well as other human cutaneous diseases. Additionally, this K01 Award will promote the career advancement of the applicant and help him to achieve research independence.

描述(申请人提供)：P.I.最近进入皮肤自身免疫的研究领域。他的职业发展计划旨在获得该领域的高级培训，并为他在他的导师L.A.迪亚兹博士的指导下成为一名独立调查员做好准备。迪亚兹博士是国际公认的皮肤病领域的领导者。为了加强培训，该项目征集了一个咨询委员会的专业知识，该委员会由在皮肤生物学、自身免疫和过敏以及生物统计学领域拥有专业知识的资深调查人员组成，以提供科学和职业建议。P.I.一直在研究自身抗体在地方性天疱疮(FS)、非地方性叶状天疱疮(PF)和寻常型天疱疮(PV)中的发生机制。他专注于在这些患者中发现的致病性抗桥粒芯糖蛋白1(DSG1)自身抗体的启动和发展。这项资助探索了自体反应性IgE抗体和致病性lgG4自身抗体在FS中的相互作用。我们实验室最近的工作表明，FS患者的抗DSGL IgE抗体水平明显高于健康对照组。我们假设FS中的lgG4和IgE抗DSGL自身抗体反应是由相同的环境抗原(“过敏原”)触发的。候选人近期的研究计划是提供证据，证明FS中的IgE和lgG4自身抗体反应与疾病的发病机制有关。目的1重点研究FS患者和来自FS流行区的健康人的IgE和lgG4抗DSGL反应的相互作用。在目的2中，我们将制备抗DSGL-IgE的单抗，以研究其V基因的用途，并通过“克隆性标记”来分析同一FS患者中抗-DSGL-lgG4抗体与IgE自身抗体之间是否存在遗传关系。在目的3中，我们将通过被动转移小鼠模型来确定抗DSGL IgE抗体的致病力。该项目的成功完成将有助于我们了解FS的病因和发病机制，以及其他人类皮肤病。此外，这一K01奖项将促进申请者的职业发展，并帮助他实现研究独立。