Immunogenicity of Homologous Heart Valves: Mechanisms and Future Considerations

Abstract

Pediatric valvar heart disease continues to be a topic of interest due to the common and severe clinical manifestations. Problems with heart valve replacement, including lack of adaptive valve growth and accelerated structural valve degeneration, mandate morbid reoperations to serially replace valve implants. Homologous or homograft heart valves are a compelling option for valve replacement in the pediatric population but are susceptible to structural valve degeneration. The immunogenicity of homologous heart valves is not fully understood, and mechanisms explaining how implanted heart valves are attacked are unclear. It has been demonstrated that preservation methods determine homograft cell viability and there may be a direct correlation between increased cellular viability and a higher immune response. This consists of an early increase in human leukocyte antigen (HLA)-class I and II antibodies over days to months posthomograft implantation, followed by the sustained increase in HLA-class II antibodies for years after implantation. Cytotoxic T lymphocytes and T-helper lymphocytes specific to both HLA classes can infiltrate tissue almost immediately after implantation. Furthermore, increased HLA-class II mismatches result in an increased cellmediated response and an accelerated rate of structural valve degeneration especially in younger patients. Further long-term clinical studies should be completed investigating the immunological mechanisms of heart valve rejection and their relation to structural valve degeneration as well as testing of immunosuppressant therapies to determine the needed immunosuppression for homologous heart valve implantation.

Partial heart transplantation: Growing heart valve implants for children

“…Firstly, heart valves appear to enjoy a degree of immune privilege. 84,85 For example, the outflow valves of orthotopic heart transplants are histologically 12,36 and functionally 86 spared from rejection. Secondly, the risk from an immune response to a partial heart transplant is far less than the risk of an orthotopic heart transplant.…”

“…The optimal level of immunosuppression for partial heart transplants is less stringent than orthotopic heart transplants. Firstly, heart valves appear to enjoy a degree of immune privilege 84,85 . For example, the outflow valves of orthotopic heart transplants are histologically 12,36 and functionally 86 spared from rejection.…”

“…Secondly, the risk from an immune response to a partial heart transplant is far less than the risk of an orthotopic heart transplant. While acute rejection of an orthotopic heart transplant is potentially life‐threatening, withdrawing immunosuppression from a partial heart transplant would merely transform it into a homovital homograft 8,46,85 …”

“…While acute rejection of an orthotopic heart transplant is potentially life-threatening, withdrawing immunosuppression from a partial heart transplant would merely transform it into a homovital homograft. 8,46,85…”