IMMUNODOMINANT OVARIAN ANTIGENS INVOLVED IN PREMATURE OVARIAN FAILURE

与卵巢早衰相关的免疫显性卵巢抗原

• 批准号: 7231552
• 负责人: JOHN C HERR
• 金额: $ 7.58万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-07 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7231552
• 关键词: Addison' s disease; Adrenal Glands; Age; Antibodies; Antigen Targeting; Antigens; Area; Assisted Reproductive Technology; Autoantibodies; Autoantigens; Autoimmune Diseases; Autoimmune Process; Autoimmune oophoritis; Autoimmunity; Biological Assay; Biological Markers; Biopsy; Blood; Caliber; Candidate Disease Gene; Clinical; Couples; Databases; Depth; Diagnosis; Diagnostic; Disease; Egg Proteins; Embryo Transfer; Enzyme-Linked Immunosorbent Assay; Estradiol; Failure; Fertility; Fertilization in Vitro; Follicle Stimulating Hormone; Functional disorder; Gel; Gene Proteins; Genes; Goals; Gold; Human; Immunoblotting; Immunohistochemistry; Immunologics; Immunotherapy; Incidence; India; Infertility; Infiltration; Invasive; Laboratories; Lead; Length; Libraries; Lymphocyte; Lymphocytic Infiltrate; Mass Spectrum Analysis; Menopause; Menstrual cycle; Methods; Mus; Oocytes; Ovarian; Ovarian Diseases; Ovarian Follicle; Ovary; Pathogenesis; Pathology; Patient Selection; Patients; Peptides; Pregnancy Rate; Premature Menopause; Premature Ovarian Failure; Prevalence; Procedures; Process; Proteins; Proteomics; Publishing; Recombinants; Reporting; Research Personnel; Research Proposals; Role; Rosa; Secondary to; Serum; Shipping; Ships; Site; Spottings; Staging; Standardization; Standards of Weights and Measures; Syndrome; System; Technology; Testing; Woman; Yeasts; base; cDNA Library; design; diagnosis standard; egg; endometriosis; follow-up; improved; interest; reproductive function; response; tool

DESCRIPTION (provided by applicant): This research proposal will characterize dominant ovarian antigens recognized by serum antibodies from patients with premature ovarian failure (POF) with the goals of better understanding the pathophysiology of POF and identifying biomarkers for diagnosis of autoimmune ovarian disease. Sera from patients with POF will be screened for antiovarian antibodies and then employed on 2-D gel immunoblots to identify immunoreactive proteins present in human and mouse ovarian and egg extracts. Immunoreactive ovarian and egg proteins will be microsequenced to identify candidate genes encoding ovarian and egg antigens. Peptide microsequences obtained by mass spectrometry will be compared to gene and protein databases to identify autoantigens. Full length cDNAs corresponding to ovarian/egg autoantigens will be cloned and recombinant antigens expressed in bacterial and yeast expression systems. The incidence of antibodies to one or more defined recombinant egg target antigens will then be determined in patients with POF and antiovarian antibodies. The studies are anticipated to lead to a deeper understanding of ovarian autoimmunity in humans and to improved methods of detecting antiovarian antibodies including the possibility of detecting early stage disease. Availability of better diagnostics for ovarian disease may also help in proper clinical follow up and selection of patients who may benefit from immunotherapy or assisted reproductive technologies (in vitro fertilization/embryo transfer [IVF/ET]) to recover their fertility.

描述（由申请人提供）：本研究计划将表征卵巢早衰（POF）患者血清抗体识别的显性卵巢抗原，目的是更好地了解POF的病理生理学，并确定自身免疫性卵巢疾病诊断的生物标志物。POF患者的血清将被筛选抗卵巢抗体，然后在二维凝胶免疫印迹上鉴定人类和小鼠卵巢和卵子提取物中存在的免疫反应蛋白。免疫反应性卵巢和卵子蛋白将进行微测序，以确定编码卵巢和卵子抗原的候选基因。质谱法获得的肽微序列将与基因和蛋白质数据库进行比较，以识别自身抗原。克隆卵巢/卵子自身抗原对应的全长cdna，并在细菌和酵母表达系统中表达重组抗原。一种或多种确定的重组卵靶抗原抗体的发生率将在POF和抗卵巢抗体患者中确定。预计这些研究将导致对人类卵巢自身免疫的更深入了解，并改进检测抗卵巢抗体的方法，包括检测早期疾病的可能性。更好的卵巢疾病诊断也有助于适当的临床随访和选择可能受益于免疫治疗或辅助生殖技术（体外受精/胚胎移植[IVF/ET]）的患者，以恢复其生育能力。