Coronary artery disease from isolated non-H2-Determined incompatibilities in transplanted mouse hearts

Paul S. Russell, Catharine M. Chase, Joren C. Madsen, Tsutomu Hirohashi, Lynn D. Cornell, Thomas J. Sproule, Robert B. Colvin, Derry C. Roopenian

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background: Most studies of vascular disease in transplanted organs have used combinations involving disparities determined by genes of the major histocompatibility complex (MHC). This report describes examples of coronary vascular disease occurring in transplanted mouse hearts involving isolated, non-H2-determined incompatibilities. Methods: Mice, incompatible in respect of HY, H4, or H60, were selected. For H60, the incompatibility depended on breeding congenic pairs or the introduction of H60 by transgenic methods because the latter method results in more widespread expression. Transplant survival was determined, and the appearance and prevalence of coronary artery vasculopathy (CAV) was established by appropriate histologic methods. Results: Advanced changes of CAV were found at 56 days in transplants involving incompatibilities confined to HY or H4. In both combinations, skin grafts were also rejected. H60 incompatibility does not result in skin graft rejection and only a minority of heart transplants shows evidence of CAV. If heart transplants are preceded by skin grafts bearing both H60 and HY incompatibilities to promote "help" in generating immunity, H60 incompatible hearts develop advanced CAV. Heart transplants in all non-MHC categories ostensibly survive in excellent condition throughout this period despite their CAV. Conclusions: CAV can develop as a consequence of non-MHC incompatibilities alone and even when antigens are sparsely expressed on cardiac tissue. Presensitization leads to much more severe vascular disease. Human leukocyte antigen compatible kidney transplants may also develop vascular disease and patients manifesting reactivity to MHC antigens should also be more prone to develop vascular disease because of undetectable non-MHC incompatibilities.

Original languageEnglish (US)
Pages (from-to)847-852
Number of pages6
JournalTransplantation
Volume91
Issue number8
DOIs
StatePublished - Apr 27 2011

Keywords

  • Coronary artery disease
  • Heart transplant
  • Non-H2-determined incompatibilities

ASJC Scopus subject areas

  • Transplantation

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