Donor-directed HLA antibodies before and after transplantectomy detected by the luminex single antigen assay.

BACKGROUND: Donor-directed antibodies (DDA) have been shown to result in poor graft survival. This study was designed to analyze antibody appearance and patient and graft characteristics related to antibody formation in patients who lost their graft at different time points after transplantation. METHODS: Pre- and posttransplant sera of 56 DDA-negative first transplant patients were screened for human leukocyte antigen (HLA) class I and II DDA by the Luminex single antigen assay (LSA). All patients were treated with calcineurine inhibitor-based immunosuppression. RESULTS: Three of 56 patients proved DDA positive by LSA before transplantation. Eighty-one percent of the remaining 53 patients became DDA class I or II positive or both; 16% before and 84% after transplantectomy. Class I antibodies were produced in 84% and class II in 77% of the recipients. Based on time of transplantectomy, three groups were created as follows: less than or equal to 1 month, 1 to 6 months, and more than 6 months. The groups proved to be significantly different for HLA class II mismatch and acute rejection. All recipients in group 1 to 6 months proved to be DDA positive. Logistic regression analysis showed that DDA positivity for class I was related to higher donor age and donor type (nonheart beating), class II to higher donor age and class II mismatch. CONCLUSIONS: Donor-directed HLA antibodies after transplantation were demonstrated in 81% of first transplant recipients, all of whom were DDA negative by LSA before transplantation. The majority of the antibodies was found after transplantectomy. These findings may have to be taken into consideration in the allocation of organs of marginal donors such as older or nonheart beating kidneys.

Clinical relevance of pretransplant donor-directed antibodies detected by single antigen beads in highly sensitized renal transplant patients.

BACKGROUND: Highly sensitized (HS) patients (>85% panel-reactive antibodies) have a lower chance of receiving a donor kidney. Within Eurotransplant the Acceptable Mismatch (AM) program was developed to increase the chances of HS patients to receive a crossmatch-negative donor kidney. The standard crossmatch in the AM program is based on complement-dependent cytotoxicity. METHODS: In this study we wanted to determine the clinical relevance of human leukocyte antigen donor-directed antibodies (DDA) detected by the single antigen (SA) bead technique, in the pretransplant sera of HS patients transplanted in our center through the Eurotransplant AM program. RESULTS: From 34 AM patients, 27 were transplanted with 1 to 5 mismatches and 7 received a 0-mismatched graft. From the mismatched patients, retrospectively, 13 proved to possess pretransplant DDA by SA whereas 14 did not. No antibodies were found in the 0-mismatched group. Comparison of the DDA+ and DDA- patients in the human leukocyte antigen-mismatched donor/recipient combinations revealed a trend to an earlier and higher number of rejection episodes in DDA+ patients (P=0.08). No detrimental effect of DDA on graft survival was observed. CONCLUSIONS: This single-center study showed that in the AM program DDA detected by SA, and not by less-sensitive methods, may be related to acute rejection episodes but is not detrimental to long-term graft outcome. These findings question the increasing use of more-sensitive screening techniques for the allocation of organs.