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Management of children undergoing cardiac transplantation with high Panel Reactive Antibodies

Published online by Cambridge University Press:  13 December 2011

Alfred Asante-Korang ,
Jeffrey P. Jacobs ,
Jeremy Ringewald ,
Jennifer Carapellucci ,
Kristin Rosenberg ,
Daniel McKenna ,
Jorge McCormack ,
Ivan Wilmot ,
Abigail Gjeldum  and
Mayra Lopez-Cepero
...Show all authors
Alfred Asante-Korang*
Affiliation:
Division of Cardiology, All Children's Hospital, Saint Petersburg, United States of America University of South Florida (USF), Saint Petersburg and Tampa, Florida, United States of America
Jeffrey P. Jacobs
Affiliation:
Division of Cardiothoracic Surgery, All Children's Hospital, Saint Petersburg, United States of America University of South Florida (USF), Saint Petersburg and Tampa, Florida, United States of America
Jeremy Ringewald
Affiliation:
Division of Cardiology, All Children's Hospital, Saint Petersburg, United States of America
Jennifer Carapellucci
Affiliation:
Division of Cardiology, All Children's Hospital, Saint Petersburg, United States of America
Kristin Rosenberg
Affiliation:
Division of Cardiology, All Children's Hospital, Saint Petersburg, United States of America
Daniel McKenna
Affiliation:
Division of Cardiology, All Children's Hospital, Saint Petersburg, United States of America
Jorge McCormack
Affiliation:
Division of Cardiology, All Children's Hospital, Saint Petersburg, United States of America University of South Florida (USF), Saint Petersburg and Tampa, Florida, United States of America
Ivan Wilmot
Affiliation:
Division of Cardiology, All Children's Hospital, Saint Petersburg, United States of America
Abigail Gjeldum
Affiliation:
Division of Cardiology, All Children's Hospital, Saint Petersburg, United States of America
Mayra Lopez-Cepero
Affiliation:
LifeLink Immunology Lab, LifeLink Foundation, Tampa, United States of America
John Sleasman
Affiliation:
Department of Immunology, All Children's Hospital, Saint Petersburg, Florida, United States of America University of South Florida (USF), Saint Petersburg and Tampa, Florida, United States of America
*
Correspondence to: Alfred Asante-Korang, MB CHB, MRCP, Clinical Associate Professor of Pediatrics, University of South Florida College of Medicine, Pediatric Cardiology Associates, 601 5th Street South, Suite 711, Saint Petersburg, Florida, 33701, United States of America. Tel: 727-322-4852; Fax: 727-821-2461; E-mail: [email protected]
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Abstract

Highly sensitised children in need of cardiac transplantation have overall poor outcomes because of increased risk for dysfunction of the cardiac allograft, acute cellular and antibody-mediated rejection, and vasculopathy of the cardiac allograft. Cardiopulmonary bypass and the frequent use of blood products in the operating room and cardiac intensive care unit, as well as the frequent use of homografts, have predisposed potential recipients of transplants to allosensitisation. The expansion in the use of ventricular assist devices and extracorporeal membrane oxygenation has also contributed to increasing rates of allosensitisation in candidates for cardiac transplantation. Antibodies to Human Leukocyte Antigen can be detected before transplantation using several different techniques, the most common being the “complement-dependent lymphocytotoxicity assays”. “Solid-phase assays”, particularly the “Luminex® single antigen bead method”, offer improved specificity and more detailed information regarding specificities of antibodies, leading to improved matching of donors with recipients. Allosensitisation prolongs the time on the waiting list for potential recipients of transplantation and increases the risk of complications and death after transplantation. Aggressive reduction of antibodies to Human Leukocyte Antigen in these high-risk patients is therefore of vital importance for long-term survival of the patient and cardiac allograft. Strategies to decrease Panel Reactive Antibody or percent reactive antibody before transplantation include plasmapheresis, intravenous administration of immunoglobulin, and specific treatment to reduce B-cells, particularly Rituximab. These strategies have resulted in varying degrees of success. Antibody-mediated rejection and cardiac allograft vasculopathy are two of the most important complications of transplantation in patients with high Panel Reactive Antibody. The treatment of antibody-mediated rejection in recipients of cardiac transplants is largely empirical and includes the use of high-dose corticosteroids, plasmapheresis, intravenous administration of immunoglobulins, anti-thymocyte globulin, and Rituximab. Cardiac allograft vasculopathy is believed to be secondary to chronic complement-mediated endothelial injury and chronic vascular rejection. The use of proliferation signal inhibitors, such as sirolimus and everolimus, has been shown to delay the progression of cardiac allograft vasculopathy. In some non-sensitised recipients of cardiac transplants, the de novo formation of antibodies to Human Leukocyte Antigen after transplantation may increase the likelihood of adverse clinical outcomes. The use of serial testing for donor-specific antibodies after cardiac transplantation may be advisable in patients with frequent episodes of rejection and patients with history of sensitisation. Allosensitisation before transplantation can negatively influence outcomes after transplantation. A high incidence of antibody-mediated rejection and graft vasculopathy can result in graft failure and decreased survival. Current strategies to decrease allosensitisation have helped to expand the pool of donors, improve times on the waiting list, and decrease mortality. Centres of transplantation offering desensitisation are currently using plasmapheresis to remove circulating antibodies; intravenous immunoglobulin to inactivate antibodies; cyclophosphamide to suppress B-cell proliferation; and Rituximab to deplete B-lymphocytes. Similar approaches are also used to treat antibody-mediated rejection after transplantation with promising results.

Keywords

Paediatriccardiac transplantationallosensitisationhuman leukocyte antigen-antigens/antibodiesantibody-mediated rejectioncardiac allograft vasculopathy
Type
Original Article
Information
Cardiology in the Young , Volume 21 , Issue S2: A Holistic Approach to Hypoplastic Left Heart Syndrome and other evolving challenges in Pediatric and Congenital Cardiac Disease , 13 December 2011 , pp. 124 - 132
Copyright
Copyright © Cambridge University Press 2011

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