Cardiac Transplantation in Infancy

婴儿期心脏移植

• 批准号: 7686265
• 负责人: Lori J West
• 金额: $ 43.02万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7686265
• 关键词: Academic Medical Centers; Acute; Address; Adult; Affect; Age; Antibodies; Antigens; Blood Group Antigens; Blood Vessels; Cardiac; Cardiomyopathies; Child; Child Development; Chronic; Clinic; Collaborations; Competence; Condition; Congenital Heart Defects; Development; Elements; Exposure to; Goals; Heart Transplantation; Histocompatibility Antigens; Human; Immune; Immune Tolerance; Immune response; Immunity; Immunocompetence; Immunologics; Immunosuppression; Immunosuppressive Agents; Infant; Injury; Institution; Laboratories; Life; Neonatal; Newborn Infant; Organ Donor; Outcome; Patients; Pharmacotherapy; Process; Proteins; Research Personnel; Resistance; Site; T-Lymphocyte; Therapeutic immunosuppression; Thinking; Thymus Gland; Toxic effect; Transplant Recipients; Transplantation; Viral; early childhood; improved; indexing; infancy; infant outcome; novel strategies; prevent; response

Heart transplantation during early childhood is a life-saving therapy for congenital cardiac malformations and cardiomyopathies that would otherwise be lethal. The two most important obstacles to providing this therapy effectively are lack of sufficient donor organs and the need for life-long immunosuppressive drug therapy. Immunosuppression effectively prevents acute cellular rejection in most patients, but may not prevent chronic vascular rejection and may cause toxicity for young children. Novel strategies, especially ABO-incompatible transplantation, to expand the donor pool for infants and children, and development of immunologic manipulations to induce tolerance to the cardiac graft donor would effectively address these hurdles. The overarching goal of this project is the study of immune processes after cardiac transplantation in infancy. We will explore whether neonatal tolerance and accommodation occur in the human setting, and which mechanisms may underlie these processes. These goals will be sought by studying patients from our institution and Loma Linda University Medical Center. We will study the immunocompetence of infant transplant recipients through the Laboratory Core at the Mayo Clinic site and through collaborations with Dr. Cascalho (Project 2) and Dr. Platt Project 3). Potential strategies to improve outcomes from infant transplantation will be explored in collaboration with Dr. Zhong (Project 4).

儿童早期心脏移植是先天性心脏病的一种挽救生命的治疗方法 畸形和心肌病，否则会致命。有效提供这种治疗的两个最重要的障碍是缺乏足够的供体器官和需要终身免疫抑制药物治疗。免疫抑制有效地防止了大多数患者的急性细胞排斥反应，但可能无法防止慢性血管排斥反应，并可能对幼儿造成毒性。新的策略，特别是ABO血型不合的移植，以扩大婴儿和儿童的供体库，以及免疫操作的发展，以诱导对心脏移植供体的耐受性，将有效地解决这些障碍。该项目的首要目标是研究婴儿心脏移植后的免疫过程。我们将探讨新生儿的耐受性和适应性是否发生在人类环境中，以及这些过程的机制可能是什么。这些目标将通过研究我们机构和洛马琳达大学医学中心的患者来实现。我们将通过马约诊所中心的实验室核心以及与Cascalho博士（项目2）和Platt博士（项目3）的合作研究婴儿移植受者的免疫能力。将与钟博士（项目4）合作探索改善婴儿移植结局的潜在策略。