Studies of major histocompatibility complex class I/II expression on sequential human heart biopsy specimens after...

Our previous data indicate that normal human cardiac myocytes do not express detectable levels of major histocompatibility complex (MHC) class II gene products and express only low levels of MHC class I gene products. Examination of heart biopsy samples after transplantation with immunoperoxidase techniques revealed that such myocytes are induced to express high levels of MHC class I/II gene products and that the expression of these gene products appeared to precede histologic evidence of rejection. In efforts to objectively quantitate the level of MHC antigen expression on sequential heart biopsy samples, a radioimmunoassay was set up. Monoclonal antisera was used against human monomorphic MHC class I and II determinants. In addition, to control for the variability in the quantity of biopsy sample, use was made of a monoclonal antisera against human cardiac myosin. A series of three to four sections (4 micron each) of the heart biopsy specimen was treated with each antisera, followed by affinity purified and absorbed iodine 125-labeled goat antimouse immunoglobulin. The mean counts per minute of MHC class I and II was divided by the mean counts per minute obtained with anti-myosin and an index of MHC class I/II derived. Data using such a radioimmunoassay indicate that MHC antigen expression on the heart biopsy specimens does not strictly correlate with histologic rejection grade scores, levels of leukocyte infiltrate, or the immunophenotype of the infiltrating mononuclear cells. Of interest was the finding that an increase in the level of MHC antigen expression occurred before histologic evidence of rejection grades of 3 or greater. In addition, MHC class I antigen expression appeared to increase in heart biopsy samples early during the post-transplant period, followed sequentially by an increase in the level of MHC class II antigen expression. Rejection episodes later during the posttransplant period, however, were accompanied by increased levels of MHC class II antigens. A kinetic analysis of the increase in the levels of MHC class I and II antigens on heart biopsy samples may not only provide a refinement of the histologic scoring of heart biopsy samples for rejection but may also suggest the use of different chemotherapeutic immunosuppressive drug regimens for the treatment of MHC class I as compared with MHC class II dependent rejection episodes.