Marilena Gregorini1,2, Claudia Del Fante3, Eleonora Francesca Pattonieri2, Maria Antonietta Avanzini4, Maria Antonietta Grignano2, Irene Cassaniti5, Fausto Baldanti5,6, Giuditta Comolli5,7, Angela Nocco8, Miriam Ramondetta8, Gianluca Viarengo3, Vincenzo Sepe2, Carmelo Libetta1,2, Catherine Klersy9, Cesare Perotti3, Teresa Rampino2. 1. Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy. 2. Unit of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy. 3. Immunohematology and Transfusion Service, IRCCS Policlinico San Matteo, 27100 Pavia, Italy. 4. Immunology and Transplantation Laboratory, Cell Factory, Pediatric Hematology Oncology, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, Italy. 5. Molecular Virology Unit, Department of Microbiology and Virology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy. 6. Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy. 7. Experimental Research Laboratories, Biotechnology Area, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, Italy. 8. Laboratory of Transplant Immunology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico Milano, 20122 Milano, Italy. 9. Clinical Epidemiology and Biometry Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy.
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.
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 ABMRpatients. 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.