Antibody-mediated rejection (ABMR) at early or late post-transplantation remains challenging. We performed a single-center single-arm study where four cases of acute ABMR and nine cases of chronic active ABMR (defined by Banff classification) were treated with double-filtration plasmapheresis (two cycles of three consecutive daily sessions with a 4-day gap between). At the end of the third and sixth DFPP sessions, the patients received rituximab 375 mg/m . After a median follow-up of 1078 (61-1676) days, kidney-allograft survival was 50%. Before DFPP/rituximab therapy, the median donor-specific alloantibody (DSA) mean fluorescence intensity (MFI) was 9160 (4000-15 400); 45 days (D45) later it had significantly decreased to 7375 (215-18 100) (P = .018). In addition, at one-year (Y1) post-therapy, MFI had decreased further, that is, 4060 (400-7850) (P = .001). In two patients, DSA MFIs decreased and remained below 2000. The slope of estimated glomerular-filtration rate within the 6 months preceding intervention was -1.18 mL/min/month and remained unchanged at -1.29 mL/min/month within the year after intervention. Proteinuria remained unchanged. Baseline Banff scores on repeat allograft biopsies (post-therapy D45, Y1) did not show any improvement. Side-effects were mild to moderate. We conclude that the combined DFPP/rituximab significantly decreased DSAs in ABMR kidney-transplant recipients but did not improve renal function or renal histology at 1-year follow-up.
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Front Immunol
January 2025
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Donor-specific antibodies (DSAs) targeting mismatched human leukocyte antigen (HLA) molecules are one of the principal threats to long-term graft survival in solid organ transplantation. However, many patients with long-term circulating DSAs do not manifest rejection responses, suggesting a degree of heterogeneity in their pathogenicity and related functional activity. Immunologic risk stratification of transplant recipients is complicated by challenges intrinsic to defining alloantibody responses that are potentially pathogenic versus those that are not.
View Article and Find Full Text PDFJ Heart Lung Transplant
December 2024
Van Cleve Cardiac Regenerative Medicine Program, Mayo Clinic, Rochester MN, 55905; Deparment of Cardiovascular Medicine, Mayo Clinic, Rochester MN, 55905. Electronic address:
Background: Although recommended in International Society for Heart and Lung Transplantation (ISHLT) guidelines, transition to mammalian targets of rapamycin (mTOR) inhibitors in heart transplant recipients is not routinely performed, in part due to perceived risk of rejection. This study sought to evaluate the incidence and risk factors for biopsy-proven, clinically relevant rejection following conversion from calcineurin inhibitor (CNI) to sirolimus (SRL) immunosuppression.
Methods: A single center retrospective study was conducted of all consecutive adult patients who underwent orthotopic heart transplantation (OHT) and CNI-free SRL conversion from January 1999 to January 2023.
Sci Transl Med
January 2025
Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Current desensitization and maintenance immunosuppression regimens for kidney transplantation in sensitized individuals show limited ability to control the posttransplant humoral response, resulting in high rates of antibody-mediated rejection (ABMR) and graft failure. Here, we showed that anti-CD154 monoclonal antibody (mAb)-based immunosuppression more effectively controlled allograft rejection and humoral rebound in a highly sensitized nonhuman primate kidney transplantation model compared with tacrolimus-based standard-of-care (SOC) immunosuppression. Desensitization with an anti-CD154 mAb (5C8) and a proteasome inhibitor led to decreased donor-specific antibodies (DSAs) and disruption of lymph node germinal centers with reduction of proliferating, memory, and class-switched B cells as well as T follicular helper cells.
View Article and Find Full Text PDFFront Transplant
December 2024
Duke Transplant Center, Duke University School of Medicine, Durham, NC, United States.
Objective: Cardiac Allograft Vasculopathy (CAV), a process of vascular damage accelerated by antibody-mediated rejection (AMR), is one of the leading causes of cardiac transplant failure. Proteasome inhibitors (PIs) are utilized to treat AMR, however PI-associated toxicity limits their therapeutic utility. Novel immunoproteasome inhibitors (IPIs) have higher specificity for immune cells and have not been investigated for AMR in cardiac transplant patients.
View Article and Find Full Text PDFFront Immunol
December 2024
Institute of Transplantation Medicine, The Second Affiliated Hospital of Guangxi Medical University, Guangxi Clinical Research Center for Organ Transplantation, Guangxi Key Laboratory of Organ Donation and Transplantation, Nanning, Guangxi, China.
Objective: This study aims to assess the efficacy of pharmacological interventions in mitigating graft injury in transplant patients with antibody-mediated rejection (AMR) through a network meta-analysis (NMA).
Methods: A search was conducted on databases such as Cochrane Library, PubMed, EmBase, and Web of Science for randomized controlled trials (RCTs) on pharmacological interventions for alleviating graft injury following AMR. The search was performed for publications up to April 12, 2024.
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