How to Grade Immunological Risk Using Sensitive HLA Donor-Specific Antibodies Detection Techniques

Since the pioneering work of Patel and Terazaki, the presence of an antidonor antibody of the IgG isotype, as demonstrated by a lymphocytotoxic assay on T-cells, has been a contraindication to transplantation due to the very high rate of graft loss reported. The advent of more sensitive and specific techniques of detection of anti-HLA antibodies (ELISA or Luminex) has questioned this dogma, with a number of reports showing that transplantation, despite the presence of a donor-specific antibody, could be done without excessive graft losses, despite higher rates of rejection. We analyzed the results of a prospective observational study on the occurrence of acute antibody-mediated rejection and survival of patients and grafts, in kidney transplant patients with preexisting donor-specific HLA antibodies detected by Luminex. This study assess, for the first time, kidney graft survival and the gradation of the risk of acute antibody-mediated rejection according to the levels of donor-specific antibodies detected before transplantation. We have shown a dramatic increase in the risk of antibody-mediated rejection with increasing levels of preexisting donor-specific antibodies above 465 as detected by Luminex. We have also shown that patients transplanted with donor-specific antibody mean fluorescence intensity > 3,000 have a 3.8 increased risk of graft loss as compared to patients transplanted with donor-specific antibody mean fluorescence intensity < 3,000 (95% CI: 3.5-18.4; p < 0.0001). This stratification of immunological risk should be used to define acceptable graft and therapeutic strategies in sensitized patients on the waiting list. Thus, the matching of graft donors and recipients should take into account this precise analysis of the immunological profile of patients and the evaluation of the risk/benefit balance. (Trends in Transplant. 2010;4:3-10)