Review ArticleImmunogenicity of Homologous Heart Valves Mechanisms and Future ConsiderationsVogel, Andrew D. MS*,†; Kwon, Jennie H. MD*; Mitta, Alekhya BS*,‡; Sherard, Curry BA*,§; Brockbank, Kelvin G. M. PhD¶,‖; Rajab, Taufiek Konrad MD* Author Information From the *Department of Surgery, Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, SC †Department of Surgery, Alabama College of Osteopathic Medicine, Dothan, AL ‡Department of Surgery, School of Medicine, University of South Carolina, Columbia, SC §Department of Surgery, College of Medicine, Medical University of South Carolina, Charleston, SC ¶Department of Surgery, Tissue Testing Technologies LLC, North Charleston, SC ‖Department of Bioengineering, Clemson University, Charleston, SC. Disclosure: The authors declare no conflict of interest. Supported by grants to TKR from the American Association for Thoracic Surgery, the South Carolina Clinical & Translational Research (SCTR) Institute (NIH/NCATS Grant Number UL1 TR001450), the Brett Boyer Foundation, the Saving Tiny Hearts Society, the Emerson Rose Heart Foundation and Philanthropy by Senator Paul Campbell. Correspondence: Taufiek Konrad Rajab, MD, Division of Cardiothoracic Surgery, Medical University of South Carolina, 10 McClennan Banks Drive, SJCH 2190/MSC 918, Charleston SC 29425. E-mail: [email protected] Cardiology in Review ():10.1097/CRD.0000000000000519, January 23, 2023. | DOI: 10.1097/CRD.0000000000000519 Buy PAP Metrics 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 cell-mediated 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. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.