Sequential analysis of monomorphic and polymorphic major histocompatibility complex antigen expression in human heart...

Changes in major histocompatibility complex (MHC) antigen expression after heart transplantation were investigated in 233 cardiac allograft biopsy specimens of 33 patients by means of immunohistologic examination. The altered tissue expression was related to histopathologic and clinical diagnoses. A panel of monoclonal antibodies directed to monomorphic determinants was used for the analysis of MHC antigens, class I (human leukocyte antigens [HLA]-A, B, C, and beta 2 microglobulin) and class II (HLA-DR, HLA-DP, HLA-DQ). Donor and recipient MHC antigen expression (HLA-A and HLA-B) was studied by use of monoclonal antibodies directed to polymorphic epitopes. It was found in 57 of 78 rejection episodes that the induction of class I MHC antigens on the normally negative myocyte membranes was related to the rejection process. Usually the induction was focally associated with lymphocytic infiltrates but in severe rejection was generalized on all myocyte membranes. After effective rejection treatment the class I induction was reversed. Class II (HLA-DR) MHC antigens were induced on most vessel endothelia. During rejection MHC antigens HLA-DP and HLA-DQ also were coexpressed on the endothelia of a few vessels. Donor HLA-A and HLA-B antigens were expressed by endothelial and interstitial cells in comparable density but only in low amounts on myocyte membranes. Recipient interstitial cells infiltrated around vessels with time after transplantation. Most interstitial cells between myofibrils, however, remained those of the donor type until 1 year after transplantation. These results show that cardiac allografts undergo remarkable changes in the expression of MHC antigens during clinical complications after transplantation. Furthermore, the changes in alloantigen composition may influence the clinical course.