Targeted monitoring of donor-specific HLA antibodies following renal transplantation

Abstract

Development of de novo donor-specific anti-HLA antibody (DSA) with antibody-mediated rejection (AMR) is the most important cause of renal allograft loss. Therefore, DSA monitoring might identify grafts susceptible to chronic humoral injury. However, implementing universal monitoring is logistically difficult, costly, and not yet supported by management guidelines, especially in patients with stable graft function. To gain further insight into humoral alloimmunity in transplant patients, we conducted a single center, retrospective study of AMR due to de novo DSA. We excluded patients without full characterization of the HLA specificities by single antigen solid phase immunoassay, and those where the clinical relevance of the DSA could not be determined. The clinical scenarios preceding AMR, HLA mismatches and alloantibody specificities, the histopathological phenotypes, and graft outcome were studied. We identified 44 renal transplant recipients with indication and protocol biopsies (44 biopsies for cause and 2 protocol biopsies), revealing 46 episodes of AMR and DSA (2 episodes in two patients). Most were late (more than 6 months after transplant). Suboptimal immunosuppression was an important prelude, usually due to non-adherence. DSA to DQ was prevalent and most biopsies were C4d positive. In all, 20 graft losses were attributed to AMR. From this study, we propose DSA monitoring in the patients with the following: (1) an episode of late (> 6 months) rejection; (2) history of non-adherence to immunosuppression; (3) immunosuppression minimization; (4) a class II loci (DR and DQ) mismatch transplant; or, (5) history of previous transplants. Close surveillance and protocol biopsies in those who develop de novo DSA is suggested.