PREFORMED IGG ANTIBODIES AGAINST MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II ANTIGENS ARE MAJOR RISK-FACTORS FOR HIGH-GRADE CELLULAR REJECTION IN RECIPIENTS OF HEART-TRANSPLANTATION

Background-Preformed anti-HLA antibodies reacting specifically with do nor lymphocytes have been associated with acute vascular rejection and early cardiac allograft failure. However, the effect of preformed ant i-HLA antibodies directed against allogeneic major histocompatibility complex (MHC) class I or II antigens of a donor panel on heart transpl antation outcome has not been extensively studied. Methods and Results -The study group consisted of 68 patients who received cardiac transpl ants between 1989 and 1996 and who were at high risk for developing an ti-HLA antibodies before transplantation. The effect of preformed anti bodies against allogeneic MHC class I or class II antigens on the deve lopment of early high-grade cellular rejection and on cumulative annua l rejection frequency was determined. Both patients with left ventricu lar assist devices and retransplantation candidates had a similar incr ease in the frequency of IgG anti-MHC class LI antibodies (IgG anti-II ) compared with control subjects (P<0.0001), whereas the frequency of IgG anti-MHC class I antibodies (IgG anti-I) was elevated only in pati ents with left ventricular assist devices. Pretransplantation IgG anti -II predicted early development of high-grade cellular rejection (P=0. 006) and higher cumulative annual rejection frequency (P<0.001) in bot h of these sensitized patient groups. Among retransplantation recipien ts, a match between donors 1 and 2 at HLA-A additionally predicted an earlier time to a high-grade cellular rejection. Conclusions-These res ults emphasize the importance of specifically screening heart transpla ntation candidates for the presence of IgG antibodies directed against MHC class IT molecules and suggest that strategies aimed at their red uction may have an impact on the onset and frequency of high-grade cel lular rejections after transplantation.