Photopheresis Abates the Anti-HLA Antibody Titer and Renal Failure Progression in Chronic Antibody-Mediated Rejection

SIMPLE SUMMARY: The most common cause of late allograft failure is chronic active antibody-mediated rejection (ABMR), but no effective therapy is available. Different immunosuppressive drugs in combination with procedures that remove serum antibodies have been used and the results have not shown to improve graft and patient outcome, but only an increased risk of adverse events. Extracorporeal pho-topheresis (ECP) is leukapheresis-based immunomodulatory therapy not associated with adverse effect, in which lymphocytes treat-ed with 8-methoxypsoralen (8-MOP) are irradiated with ultraviolet-A (UVA) ex vivo and re-infused into the patient. In this study we investigated therapeutic long-term effect of ECP in patients with biopsy proved chronic ABMR. ABSTRACT: Objective: Chronic renal antibody-mediated rejection (ABMR) is a common cause of allograft failure, but an effective therapy is not available. Extracorporeal photopheresis (ECP) has been proven successful in chronic lung and heart rejection, and graft versus host disease. The aim of this study was to evaluate the effectiveness of ECP in chronic ABMR patients. Patients and Methods: We investigated ECP treatment in 14 patients with biopsy-proven chronic ABMR and stage 2–3 chronic renal failure. The primary aim was to e valuate the eGFR lowering after 1 year of ECP therapy. The ECP responders (R) showed eGFR reduction greater than 20% vs the basal levels. We also evaluated the effectiveness of ECP on proteinuria, anti-HLA antibodies (HLAab), interleukin 6 (IL-6) serum levels, and CD3, CD4, CD8, CD19, NK, Treg and T helper 17 (Th17) circulating cells. Results: Three patients dropped out of the study. The R patients were eight (72.7%) out of the 11 remaining patients. Because ECP was not associated with any adverse reaction, the R patients continued such treatment for up to 3 years, showing a persisting eGFR stabilization. Twenty four hour proteinuria did not increase in the R patients over the follow-up when compared to the non-responder patients (NR). In the R patients, the HLAab levels were reduced and completely cleared in six out of eight patients when compared with the NR patients. The NR HLAab levels also increased after the discontinuation of the ECP. The ECP in the R patients showed a decrease in CD3, CD4, CD8, CD19, and NK circulating cells. The ECP treatment in the R patients also induced Tregs and Th17 cell increases, and a decrease of the IL-6 serum levels. Conclusions: ECP abates the HLAab titer and renal failure progression in patients with chronic renal ABMR, modulating the immune cellular and humoral responses.