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).

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL079067-05
Application #
7891156
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
5
Fiscal Year
2009
Total Cost
$442,015
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Urschel, Simon; West, Lori J (2016) ABO-incompatible heart transplantation. Curr Opin Pediatr 28:613-9
Cascalho, Marilia; Platt, Jeffrey L (2016) Harnessing B cells in immunotherapy. Immunotherapy 8:237-9
Dijke, Esme I; Platt, Jeffrey L; Blair, Paul et al. (2016) B cells in transplantation. J Heart Lung Transplant 35:704-10
Yamada, Chisa; Ramon, Daniel S; Cascalho, Marilia et al. (2015) Efficacy of plasmapheresis on donor-specific antibody reduction by HLA specificity in post-kidney transplant recipients. Transfusion 55:727-35; quiz 726
Platt, Jeffrey L; Wrenshall, Lucile E; Johnson, Geoffrey B et al. (2015) Heparan Sulfate Proteoglycan Metabolism and the Fate of Grafted Tissues. Adv Exp Med Biol 865:123-40
Barbosa, Rita R; Silva, Susana L; Silva, Sara P et al. (2014) Reduced BAFF-R and increased TACI expression in common variable immunodeficiency. J Clin Immunol 34:573-83
Tsuji, Shoichiro; Stein, Lucas; Kamada, Nobuhiko et al. (2014) TACI deficiency enhances antibody avidity and clearance of an intestinal pathogen. J Clin Invest 124:4857-66
Platt, Jeffrey L; Cascalho, Marilia (2013) New and old technologies for organ replacement. Curr Opin Organ Transplant 18:179-85
Cascalho, Marilia I; Chen, Brian J; Kain, Mandy et al. (2013) The paradoxical functions of B cells and antibodies in transplantation. J Immunol 190:875-9
Lynch, R J; Silva, I A; Chen, B J et al. (2013) Cryptic B cell response to renal transplantation. Am J Transplant 13:1713-23

Showing the most recent 10 out of 50 publications