Chronic antibody-mediated rejection (cAMR) has very few effective therapeutic options. Interleukin-6 is an attractive target because it is involved in inflammation and humoral immunity. Therefore, the use of tocilizumab (anti-IL6 receptor, TCZ) is a potential valuable therapeutic option to treat cABMR in kidney-transplant (KT) recipients. This single-center retrospective study included all KT recipients that received monthly TCZ infusions in the setting of cABMR, between August 2018 and July 2021. We assessed 12-month renal function and KT histology during follow-up. Forty patients were included. At 12-months, eGFR was not significantly different, 41.6 ± 17 vs. 43 ± 17 mL/min/1.73 m ( = 0.102) in patients with functional graft. Six patients (15%) lost their graft: their condition was clinically more severe at the time of first TCZ infusion. Histological follow-up showed no statistical difference in the scores of glomerulitis, peritubular capillaritis, and interstitial fibrosis/tubular atrophy (IFTA). Chronic glomerulopathy score however, increased significantly over time; conversely arteritis and inflammation in IFTA ares improved in follow-up biopsies. In our study, the addition of TCZ prevented clinical and histological worsening of cABMR in KT recipients, except for more severely ill patients. Randomized studies are needed to clarify the risk/benefit of TCZ in cABMR.
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http://dx.doi.org/10.3389/fmed.2021.790547 | DOI Listing |
Pharmaceutics
January 2025
Department of General and Transplant Surgery, Poznan University of Medical Sciences, 60-355 Poznan, Poland.
: Chronic antibody-mediated rejection (cAMR) constitutes a serious challenge in the long-term success of organ transplantation. It is associated with donor-specific antibodies (DSAs) which activate a complement pathway in response to the presence of human leukocyte antigens (HLAs) on the graft, which results in chronic inflammation and leads to graft dysfunction. One of the recent promising methods of cAMR treatment is a recombinant humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody referred to as Tocilizumab (TCZ).
View Article and Find Full Text PDFAm J Transplant
January 2025
Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan; Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. Electronic address:
Antibody-mediated rejection (ABMR) remains a leading cause of graft loss during kidney transplantation. Ischemia reperfusion injury (IRI) has been reported to promote T-cell proliferation, leading to B-cell activation and subsequent production of donor-specific antibodies (DSA), which target antigens on the vascular endothelium. We hypothesize that a novel therapeutic strategy targeting highly toxic reactive oxygen species could mitigate oxidative stress and immune responses associated with IRI.
View Article and Find Full Text PDFWorld J Gastroenterol
January 2025
Senior Department of Hematology, The Fifth Medical Center of PLA General Hospital, Beijing 100071, China.
In this article, we comment on an article published in a recent issue of the . We specifically focus on the roles of human leukocyte antigen (HLA) and donor-specific antibodies (DSAs) in pediatric liver transplantation (LT), as well as the relationship between immune rejection after LT and DSA. Currently, LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.
View Article and Find Full Text PDFJ Nephrol
January 2025
Renal Transplant Unit, Department of Nephrology and Kidney Transplantation, Hospital Clínic of Barcelona, Carrer Villaroel 170, 08036, Barcelona, Spain.
There is no established treatment for late or chronic antibody-mediated rejection of a kidney graft. Rituximab-based treatment is not effective, since long-lived high-affinity plasma cells do not express CD20 and do not depend on previous maturation steps to generate donor-specific antibodies. Conversely, daratumumab, an anti-CD38 monoclonal antibody, directly targets plasma cells, with proven efficacy in multiple myeloma.
View Article and Find Full Text PDFClin Kidney J
January 2025
Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Background: Lysinuric protein intolerance (LPI) is a metabolic disorder that leads to dysfunctional intestinal absorption and kidney clearance of cationic amino acids. Chronic kidney disease develops in many LPI patients and leads to end-stage kidney disease in at least 10% of patients. Since data on kidney transplants in LPI patients are limited, we analysed the outcomes of LPI patients after transplantation in Finland.
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