THE RELATIONSHIP AMONG DONOR-RECIPIENT HLA MISMATCHES, REJECTION, AND DEATH FROM CORONARY ARTERY DISEASE IN CARDIAC TRANSPLANT RECIPIENTS1

Abstract

Review of 448 cyclosporine-treated heart transplant recipients was undertaken to examine the relationship of donor-recipient HLA compatibility to patient survival, rejection, and death from coronary artery disease (CAD). Pre-Tx crossmatching and panel-reactive antibody (PRA) were correlated to survival as well. Overall patient survivals were 78%, 70%, and 65% at 1,3, and 5 years post-Tx, respectively. Matching of donor-recipient HLA did not improve outcome in that 1,3, and 5 years survivals for well-matched (< or = 2 A, B, or 0-1 DR mismatches [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 < or = 2 A, BMMs 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). Moreover, HLA-DR, but not HLA A, B was a significant (P < 0.01) predictor of early rejection (<30 days) in that 65% (165/254) of poorly matched vs. only 40% (95/194) of well-matched HLA-DR recipients experienced early rejections. Interestingly, an inverse relationship was found between HLA A and B MM, but not HLA-DR MM, and death from coronary artery disease in that 17% (19/11) of well matched vs 9% (32/327) of poorly matched patients died from CAD. Pre-Tx PRA did not impact patient survival or rejection. Donor-recipient crossmatching was performed utilizing the NIH and/or antiglobulin (AHG) procedures. No survival differences were observed at 1, 2, and 3 years post-Tx when comparing outcome for the 24 NIH crossmatch (XM)-positive (+) with the 424 NIH-XM-negative displayed a positive AHG recipient antidonor displayed a positive AHG recipient antidonor reactivity. When these 10 AHG-XM (+) sera were treated with dithioerythritol (to inactivate IgM) all 10 converted to a negative reactivity, indicating that a positive crossmatch due to IgM reactivity should not be considered a contraindication to 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 immunosuppressive regimen to prevent early rejections.