Anti-Donor Hla Antibodies Associated With Allograft Arteriopathy Detected Using Intravascular Ultrasound

95 Transplant (TX) associated vasculopathy remains one of the major obstacles to long-term survival after cardiac transplantation. Although it is though that immune-mediated processes play a significant role in the development of post-TX coronary artery disease, this has not been universally accepted. Here we examine this question using two sensitive techniques including flow cytometric crossmatch (FCXM), which assesses the immunologic milieu, and intravascular ultrasound (IVUS) to detect and quantify vasculopathy. Ninety-three patients who received cardiac transplants between January 1993 through December 1995 had coronary angiography and IVUS performed at the time of discharge and at yearly intervals thereafter to detect donor lesions as well as to assess both de novo lesions and progression of donor lesions. Donor disease at baseline was defined as significant if lesions were > 0.5mm; de novo were sites >0.5mm lesions at locations normal at baseline; donor progression was considered significant if there was>0.3mm change over one year. A three-color FCXM was used to quantitate anti-donor IgG reactions against both T and B lymphocytes. Reactions positive against both T and B calls were consistent with HLA Class I reactivity, and those that were B cell positive only were considered to be against Class II antigens. All patients had FCXM performed at the time of TX and serial post-TX sera were tested against donor lymphocytes in 53 patients. Thirty-nine percent of patients had de novo lesions at one year and 59% at 2 years. As seen in the table, the pre-TX FCXM was not associated with the detection of lesions at one two years. A significantly higher percentage of post-TX FCXM positive cases had lesions at one year when compared to the negative, although this difference did not reach significance at two years. While more data must be obtained to confirm this finding, it is likely that the development of antibodies against donor HLA class I antigens may be involved in the development of lesions as identified by intravascular ultrasound. It remains to be seen if more aggressive immunosuppresion in these cases might abrogate this event.