Blood transfusion induced changes in cell-mediated lympholysis: to immunize or not to immunize.

We have recently observed that the HLA-DR match between recipients and transfusion donors influences the beneficial effect of blood transfusions on allograft survival. To examine the immunologic effects of one-HLA-DR-Ag-matched and completely DR-mismatched transfusions, transfusion-induced changes in cell-mediated lympholysis (CML) were investigated. Blood donor directed CTL activity was measured in vitro before and after blood transfusion in 56 candidates for organ transplantation who received planned HLA-typed blood. We report that blood donor-directed CTL activity increased substantially after a single transfusion mismatched with the recipient for two HLA-DR Ag (p less than 0.0001). A transfusion matched for one HLA-DR Ag did not enhance CTL activity. No correlation was found between CTL reactivity and sharing of HLA class I Ag. The present study supports our previous observation that matching for at least one HLA class II Ag (HLA-DR) between transfusion recipient and blood donor is required if immunization by blood transfusion is to be avoided. These data show that the presence or absence of "autologous" HLA-DR Ag on the leucocytes of the transfusion donor plays a decisive rol whether immunization or immune suppression will ensue.

Comparison of four different cyclosporine immunoassays in heart and kidney transplant recipients.

Four different immunoassays were used to measure cyclosporine A (CsA) plasma (20 degrees C) levels in heart and kidney transplant recipients. Two radioimmunoassays (RIAs) (Sandimmune and Cyclotrac) and the fluorescence polarization immunoassay (FPIA) were based on polyclonal antibodies, whereas the fourth (Cyclotrac-SP) used a CsA-specific mouse monoclonal antibody. We found considerable differences in measured CsA concentrations, which were dependent on the method used and the clinical situation of the patient. Correlation coefficients between the nonspecific assays ranged from 0.899 to 0.901 with plasma values increasing in the order Sandimmune less than Cyclotrac less than FPIA. In the CsA-specific RIA, values were lower, and the correlation with the nonspecific assays ranged from 0.761 to 0.795. In the first 21 days posttransplantation, the heart transplant group showed a higher ratio of nonspecific/specific CsA (mean 4.0) compared with the subsequent period (mean 2.3) or with renal transplant recipients (mean 2.4). The TDX method showed the best assay characteristics. In heart transplant patients with specific and nonspecific 125I-RIA methods, mean CsA levels were 25% lower during rejection periods compared with periods without signs of rejection.

Rejection prophylaxis with sequential OKT3 and CSA after kidney transplantation.

Sixteen kidney transplant recipients received the IgG2a anti-CD3 monoclonal antibody OKT3 and azathioprine as rejection prophylaxis during the first two postoperative weeks. Concomitant immunosuppression consisted of low dose steroids while cyclosporine A therapy was instituted on day 12. Side effects included fever, bronchospasm, hypotension and diarrhoea. OKT3 caused T cell modulation resulting in CD3 dim+, CD4+ or CD8+, CD5+, WT31- and 11F2- cells. Anti-OKT3 antibodies were found in approximately 50% of the patients. The protocol induced a 100% patient and graft survival and a 81% actuarial freedom of rejection at 18 months. It prevented CsA associated nephrotoxicity in the direct postoperative phase. These beneficial effects outweighed the side effects of OKT3.

Treatment with cyclosporin and risks of graft rejection in male kidney and heart transplant recipients with non-O blood.

In a consecutive series of 146 kidney transplant recipients treated with cyclosporin A a strong correlation between matching for the HLA-A, HLA-B, and HLA-DR loci specificities and outcome of the grafts was observed in male recipients with non-O blood groups. Such a beneficial effect of matching was not found in female patients or male patients with blood group O. In these patients survival of the grafts at one year was good irrespective of the number of HLA-A, B, and DR mismatches. Also in 47 male heart transplant recipients immune responsiveness against mismatched HLA antigens was related to blood group. A significantly higher incidence of rejection episodes was observed in male patients with non-O blood groups (n = 32) than in those with blood group O (n = 15). Matching for HLA-DR reduced the number of acute rejection episodes in male patients with non-O blood. These findings may help explain the controversial reports about the importance of HLA matching in organ transplantation. Furthermore, as most candidates for heart transplantation are male and not of blood group O, the higher incidence of graft rejection in these patients underscores the need for an exchange strategy of donor hearts.

The interaction between the Lewis blood group system and HLA-matching in renal transplantation.

A retrospective study was initiated to investigate the influence of recipients' Lewis subtype and HLA-matching on cadaveric kidney graft outcome. A total of 1111 patients receiving a first cadaveric kidney graft were analyzed. No difference in one-year graft survival was found between Lewis-negative (73%, n = 133) and Lewis-positive (73%, n = 978) recipients. Further subdivision of the study group into HLA-A,-B well-matched (0 or 1 mismatches [MM]) and poorly matched (2, 3, or 4 MM) revealed a strong deleterious effect of HLA-A,-B mismatching in the Lewis-negative group only. One year graft survival in Lewis-negative HLA-A,-B poorly matched (2, 3, or 4 A,B MM) patients was 60% (n = 67) versus 86% (n = 66) in the Lewis-negative HLA-A,-B well-matched (0 or 1 A,B MM) group (P = 0.004). For the Lewis-positive group the one-year graft survival rates were 72% (2, 3, or 4 A,B MM; n = 498) and 74% (0 or 1 A,B MM; n = 480), respectively (P = n.s.). The additional beneficial effect of HLA-DR matching again turned out to be strongest in the Lewis-negative group. In Lewis-negative, HLA-DR (0 MM) and -A,-B well-matched recipients (n = 36) graft survival was 94% versus only 64% in the Lewis-negative, DR matched, A,-B mismatched (2, 3, or 4 A,B MM) group (n = 25; P = 0.09). In the Lewis-positive, HLA-DR 0 mismatched group the one-year survival rates were 78% (0 or 1 A,B MM; n = 240) and 73% (2, 3, or 4 A,B MM; n = 253), respectively (P = 0.05). Our data suggest that donor recipient selection should not be based on Lewis matching per se. However, since Lewis-negative patients are at high risk of graft failure when receiving HLA mismatched kidneys, they should preferentially receive optimally HLA matched grafts.

Prevention of CMV infection by screening for CMV antibodies in renal allograft recipients and their blood and kidney donors.

The influence of the cytomegalovirus (CMV) serostatus of blood and kidney donors on patient and graft survival was studied prospectively in 73 cadaveric renal graft recipients. Six out of 12 (50%) CMV seronegative recipients receiving a kidney from a CMV seropositive donor developed CMV disease, in contrast to none of 7 CMV seronegative donor/recipient combinations. Transmission of CMV with blood products to seronegative recipients was not observed in this study. A poor graft survival of 41% 3 years after transplantation was found in CMV seronegative recipients with CMV seropositive allograft donors, compared with an actuarial 3 year graft survival of 72% in the 7 CMV seronegative donor/recipient combinations. Six patients with graft failure had a CMV infection. This study, in accordance with other studies, suggests that selection of CMV seronegative renal allograft donors for CMV seronegative recipients will improve graft survival.

Influence of HLA matching, donor age, and cyclosporine on unrelated pediatric renal allograft survival.

Results in this study demonstrate that HLA matching has a beneficial effect on the survival of renal allograft in pediatric recipients. The introduction of a child-match procedure may have led to a lower degree of HLA well-matched grafts because of the small size of the pediatric waiting list. The poor results obtained in the group of children aged less than 6 years may have been due to a difference in physical condition at the moment of transplantation. This may explain why 4 of 20 (20%) of the failures in that age-group were due to patient death. The best results with the child-match procedure were obtained if the donor and recipient were both aged between 6 and 15 years. The overall graft survival in all children was improved by the use of Cs. An increase of approximately 10% was observed in this group of patients. The numbers in this group are too small, however, to permit any meaningful analysis of the influence of Cs on HLA matching. Finally, the overall results in this report demonstrate that renal transplantation is an effective form of therapy for end-stage renal disease in children.