Toward a solution for cardiac failure in the newborn

Abstract

The newborn infant with severe cardiac failure owed to congenital structural heart disease or cardiomyopathy poses a daunting therapeutic challenge. The ideal solution for both might be cardiac transplantation if availability of hearts was not limiting and if tolerance could be induced, obviating toxicity of immunosuppressive therapy. If one could safely and effectively exploit neonatal tolerance for successful xenotransplantation of the heart, the challenge of severe cardiac failure in the newborn infant might be met. We discuss the need, the potential for applying neonatal tolerance in the setting of xenotransplantation and the possibility that other approaches to this problem might emerge.

The five dimensions of B cell tolerance

“…30,31 These observations indicate that newborn recipients develop tolerance to the foreign blood group saccharide(s) ( Figure 2). 30,31 These observations indicate that newborn recipients develop tolerance to the foreign blood group saccharide(s) ( Figure 2).…”

“…In newborn recipients yet to develop mature B cells specific for the foreign saccharides in the graft, little or no antibody against the saccharide is detected once the B cell response matures and few or no B cells specific for the saccharide in the heart are detected in the blood. 30,31 These observations indicate that newborn recipients develop tolerance to the foreign blood group saccharide(s) ( Figure 2). However, the recipients develop normal levels of antibody and normal B cell responses to foreign saccharides not present in their transplant indicating that tolerance is "specific".…”

The “Baby Fae” baboon heart transplant—Potential cause of rejection

“…In their very thoughtful commentary discussing our paper on the possibility of achieving immunological tolerance to pig heart xenografts in neonates, 1 Jeffrey Platt and his coauthors 2 discuss the well-known transplant of a baboon heart into the patient known as Baby Fae in 1984 by Loma Linda surgeon, Leonard Bailey. 3 Despite ABO-incompatibility between patient and graft, the baboon heart functioned well for two weeks, but then underwent rejection, the baby sadly dying on day 20.…”

Xenotransplantation literature update, November/December 2018

“…As xenotransplantation rapidly approaches clinical applications, the conditions of its use must be analyzed. Infants provide an interesting setting for xenotransplantation given their undeveloped immune system; infants with heart defects requiring reconstruction or allotransplantation may be candidates for either short‐ or long‐term porcine heart grafts . Cooper et al, in their personal viewpoint, outline a strategy involving genetic engineering of pig donors, a new immunosuppressive regime, and transplants of both the defective heart and thymus.…”

“…Cooper et al, in their personal viewpoint, outline a strategy involving genetic engineering of pig donors, a new immunosuppressive regime, and transplants of both the defective heart and thymus. Theories given by Cooper et al are discussed by Platt et al alongside current practices. While pushing for the success and rapid acceptance of xenotransplantation, they provide details into the safety and efficacy of such solutions.…”