THE RELATIONSHIP AMONG DONOR-RECIPIENT HLA MISMATCHES, REJECTION, ANDDEATH FROM CORONARY-ARTERY DISEASE IN CARDIAC TRANSPLANT RECIPIENTS

Review of 448 cyclosporine-treated heart transplant recipients was und ertaken to examine the relationship of donor-recipient HLA compatibili ty to patient survival, rejection, and death from coronary artery dise ase (CAD). Pre-Tx crossmatching and panel-reactive antibody (PRA) were correlated to survival as well. Overall patient survivals were 78%, 7 0%, and 65% at 1, 3, and 5 years post-Tx, respectively. Matching of do nor-recipient HLA did not improve outcome in that 1, 3, and 5 year sur vivals for well-matched (less-than-or-equal-to 2 A, B, or 0-1 DR misma tches [MMs]) vs. poorly matched (>2 A, B, or 2 DR MMs) recipients were comparable and not significantly different. Well-matched recipients, however, experienced significantly fewer rejections (1.06+/-1.2 vs. 1. 96+/-1.0, P<0.01 for less-than-or-equal-to 2 A, B MMs vs. >2 A, B MMs and 1.1+/-0.9 vs. 2.0+/-1.1 for 0-1 DR MMs vs. 2 DR MMs, P<0.01). More over, HLA-DR, but not HLA A, B, was a significant (P<0.01) predictor o f early rejection (<30 days) in that 65% (165/254) of poorly matched v s. only 40% (95/194) of well-matched HLA-DR recipients experienced ear ly rejections. Interestingly, an inverse relationship was found betwee n HLA A and B MM, but not HLA-DR MM, and death from coronary artery di sease in that 17% (19/111) of well-matched vs. 9% (32/327) of poorly m atched patients died from CAD. Pre-Tx PRA did not impact patient survi val or rejection. Donor-recipient crossmatching was performed utilizin g the NIH and/or antiglobulin (AHG) procedures. No survival difference s were observed at 1, 2, and 3 years post-Tx when comparing outcome fo r the 24 NIH cross-match (XM)-positive (+) with the 424 NIH-XM-negativ e patients. Only 10 patients (10/125 AHG-tested recipients) displayed a positive AHG recipient antidonor reactivity. When these 10 AHG-XM () sera were treated with dithioerythritol (to inactivate IgM) all 10 c onverted to a negative reactivity, indicating that a positive crossmat ch due to IgM reactivity should not be considered a contraindication t o cardiac transplantation. These data also suggest that the reactivity of the 24 NIH-XM(+) sera were most likely due to IgM, and that poorly matched heart recipients may benefit from a more aggressive immunosup pressive regimen to prevent early rejections.