Association of HLA-DR Antibodies and Graft Rejection in Renal Transplantation: Posttransplant Analysis Using the Monoclonal Antibody-Specific Immobilization of Leukocyte Antigens Assay (MAILA)

Abstract

Background: The clinical impact of HLA-DR alloantibodies in renal transplantation is still controversial. This may be partly due to the lack of specificity and sensitivity of current detection methods, e.g. complement-dependent cytotoxicity test employing B lymphocytes as target antigens. Patients and Methods: In this study, we analyzed the incidence and specificity of HLA-DR antibodies after renal transplantation by use of the antigen-specific capture assay MAILA. 53 primary cadaver kidney recipients were recruited for a prospective study and were retrospectively assigned to the following groups: 20 patients with unsuspicious clinical course within the first 3 months after transplantation (control group), 20 patients undergoing histologically proven acute rejection within the first 3 months after transplantation, and 13 patients with chronic rejection 1 year or later after transplantation. 105 patients’ sera collected prospectively were analyzed by MAILA using 13 homozygous B-lymphoblastoid cell lines (B-LCL) carrying the common HLA-DR specificities. Results: In the control group, only 1 of 19 patients (5.3%) without acute rejection revealed HLA-DR antibodies after transplantation. In contrast, HLA-DR alloantibodies could be detected post transplant in 36.8% (7/19) and 69.2% (9/13) of patients with acute and chronic rejection, respectively. The frequency of HLA-DR antibodies present in both study groups was significantly higher in comparison to the control group. Of the 17 patients who received a graft across a donor recipient HLA-DR mismatch, 5 patients exhibited donor-specific alloantibodies. However, the majority of antibodies detected was not specific for mismatched HLA-DR alloantigens. Conclusion: HLA-DR antibodies were significantly associated with transplant rejection in first cadaver renal transplantation, especially in patients undergoing chronic rejection. Although donor specificity was not observed in the majority of patients, monitoring of HLA-DR antibodies might support diagnosis of graft rejection.