Immunosuppression Related to De Novo Donor-Specific HLA Antibody Production after Renal Transplantation

Abstract

Aim One of the major factors influencing graft loss is antibody-mediated rejection caused by the production of donor-specific HLA antibodies (DSA). The optimization of multidrug combination therapy using immunosuppressants is required in order to prevent DSA production. We herein evaluated the relationships among clinical variants including immunosuppressant levels and the prediction of DSA production after renal transplantation (Tx). Methods Living renal transplant patients (n=160) at our institute who received standard immunosuppressant protocols with basiliximab, tacrolimus (Tac), mycophenolate mofetil (MMF), and steroids between July 2004 and September 2013 were enrolled. The production of serum anti-HLA antibodies at one-year post-Tx was analyzed by solid-phase bead-based assays using Luminex. The HLA specificity of DSA was evaluated based on the data of donor HLA typing. In the present study, preformed DSA and de novo DSA were defined as those detected pre-Tx and at one-year post-Tx, and those detected at one-year post-Tx only, respectively. Risk factors for DSA production were statistically evaluated using clinical variables including Tac trough levels and the incidence of virus infections. Results DSA production at one-year post-Tx was observed in 15 patients including 9 with preformed DSA and 7 with de novo DSA. Preformed and de novo DSA were detected in one patient. De novo DSA production was more likely to occur in patients with low serum Tac levels (cut-off value: 3.2 ng/mL), in those who ceased MMF medication, and in those who acquired CMV infection within one-year post-Tx (p=0.008, 0.044, and 0.050, respectively). Conclusions The appropriate control of Tac trough levels, continuation of MMF intake, and prevention of CMV infection were found to be important for avoiding de novo DSA production at one-year post-Tx in the present study.