Cardiac Transplantation in Infancy

儿童早期心脏移植是治疗先天性心脏病的一种救命方法 畸形和心肌病，否则将是致命的。有效提供这种疗法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。在大多数患者中，免疫抑制有效地防止了急性细胞排斥反应，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，扩大婴儿和儿童的供体池，以及开发免疫操作以诱导对心脏移植物供者的耐受，将有效地解决这些障碍。该项目的首要目标是研究婴儿期心脏移植后的免疫过程。我们将探讨新生儿的耐受和适应是否发生在人类环境中，以及哪些机制可能是这些过程的基础。这些目标将通过对我们机构和洛马琳达大学医学中心的患者进行研究来实现。我们将通过梅奥诊所的实验室核心以及与卡斯卡略博士(项目2)和普拉特博士项目3的合作，研究婴儿移植受者的免疫能力。将与钟博士合作探索改善婴儿移植结果的潜在策略(项目4)。

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).