Abrogation of Antibodies Improves Outcome of Renal Transplantation

Abstract

IntroductionAntibodies are known to cause rejection and therefore are detrimental to graft survival. We describe two protocols of clonal stimulation deletion (CSD) pretransplant followed by grafting with no conventional immunosuppression (IS). MethodsCSD was employed in 54 patients of mean age, 28.7 years and mean human leukocyte antigen A/B/DR match, 3.25. The two protocols both employed stimulation with donor-specific transfusions and stem cells with deletion using total lymphoid irradiation in group 1 (n = 29) or bortezomib in group 2 (n = 25). Other adjuvants in both protocols were cyclophosphamide, rabbit antithymocyte globulin, and rituximab. Stimulation and deletion were monitored by lymphocyte crossmatches and detection of donor-specific antibodies (DSA). Posttransplant monitoring included serum creatinine (SCr) measurements and antibody detection at regular intervals. Graft biopsy performed in the event of dysfunction was managed by standard guidelines. Rescue IS was initiated upon a rise in SCr or DSA. ResultsMean follow-up in group 1 is 3.28 years and 2.11 years in group 2. There was 100% graft and patient survivals in both cohorts with 23 patients without IS and stable graft function with an SCr of 1.3 mg/dL. All acute rejection episodes, which occurred among 24.1% of group 1 and 20% of group 2, were rescued with therapy evolving as a SCr of 1.6 to 1.9. The majority of rejections were antibody-combined with T-cell-mediated responses. We did not observe untoward effects of the protocol. ConclusionAbrogation of antibodies improved renal transplant outcomes.