View clinical trials related to Antibody-mediated Rejection.
Filter by:The goal of this clinical trial is to evaluate the therapeutic effect of extracorporeal photopheresis in subclinical antibody-mediated rejection after lung transplantation.The main questions it aims to answer are: 1. Does ECP therapy result in a significant reduction in MFI (Mean Fluorescence Intensity) from the baseline MFI in clinically stable patients with persistent (>6 months) dnDSAs (MFI>1000)? 2. What is the impact of ECP therapy on the following outcomes in these patients: ACR, clinical AMR, CLAD, infections, drop-out rate, survival, adverse events? Participants will be randomized into two groups. Each group will include 40 patients. The control group will be observed and no active treatment will be administered. The treatment group will receive extracorporeal photopheresis. First, a two-day treatment cycle will be performed once every second week for the first two months. Then, a two-day treatment cycle will be performed once a month for 6 months. Researchers will compare the two groups regarding: MFI value, development of ACR, clinical AMR, CLAD, infections, survival, adverse events, immunophenotyping, miRNA expression profiling, cytokine expression, gene expression signature of PBMCs and proteomic characterization.
Renal transplantation is the best choice for the treatment of end-stage renal disease, but the long-term survival of the graft is still remains a challenge. Chronic antibody-mediated rejection (AMR) is the main factor affecting the long-term survival of the graft. There is still no effective treatment for chronic antibody-mediated rejection, even in the active phase (CaAMR). In recent years, new therapeutic drugs based on the generation of DSA and the mechanism of AMR, including protease inhibitor bortezomi, CD20 monoclonal antibody, C5 monoclonal antibody and IL-6 antibody, have not been able to effectively eliminate and inhibit the generation of DSA, nor have they been proved to have a definite effect on AMR. CD38 is a type II transmembrane protein that is highly expressed on plasma cells and NK cells, which are considered to play a key role in the occurrence and development of AMR. Recently, a few cases have reported that CD38 monoclonal antibody combined plasma exchange and/or IVIG may be an effective strategy for the prevention and treatment of AMR, but the effectiveness and safety of daratumumab monotherapy on CaAMR were unknown. This is a multicenter, prospective, single arm clinical study. The study will enroll 15 renal transplant recipients with positive DSA and CaAMR confirmed by biopsy after renal transplantation. According to inclusion and exclusion criteria patients will be screened to participate in the trial.
Rationale: Despite improved patient and graft survival in renal transplant recipients, still 20% of the patients reaches end-stage renal disease within 5 years after transplantation. Antibody-mediated rejection (ABMR) is one of the major causes of early graft loss and perhaps even more important of late deterioration of graft function Objective: Evaluate the occurrence of antibody mediated rejection (ABMR) and mixed ABMR and cellular/ T-cell mediated rejection (TCMR), in patients treated with the currently prevailing immunosuppressive regimens, and relate them to outcome (graft survival, function, proteinuria, histology) Study design: Clinical cohort study. Study population: patients of >18 years old, about to receive a post mortal of living donor renal transplant with an immunological high risk for ABMR. Main study parameters/endpoints: main study endpoints are the occurrence of ABMR, mixed ABMR/TCMR and renal function after 1 year of follow-up. The main study parameter will be mapping the immune system, including B-cells, (non-)HLA antibodies, interaction between B-cells and T follicular helper cells, and complete immune profiling.
Patients who have immune mediated diseases commonly undergo plasma exchange (PLEX) procedures to remove pathological substances, typically believed to be antibodies. At our facility about 400 of these procedures are performed annually on 40-60 different patients. These procedures are considered within the standard of care for these patients and are covered by insurance. This study will not influence the treatment plan for subjects who participate in this study. The goal of the study is to collect and cryopreserve blood biospecimens (plasma, serum, PBMCs) for current and future studies. Any patient undergoing plasma exchange procedures will be eligible for the study. Patients or the legally authorized representative (LAR) will be consented for the study as soon as feasible after the are referred to DeGowin for plasma exchange. The immediate objective of the study is to examine antibody levels (IgG/IgM) and BAFF levels in the blood of these patients over the course of the plasma exchange treatments. Specimens and clinical data will be collected such that other immune factors that may regulate B cell survival, proliferation and antibody secretion can be studied. Another goal of the study is to isolate and cryopreserve PBMCs at different points during the patient's treatment. This would allow the study of immune cells that may mediate these diseases. The study will also follow pathological antibodies over time in these patients so biospecimens can be obtained even after the completion of their course of plasma exchange treatments. The collection of biospecimens and clinical information from these subjects will help us understand the impact of plasma exchange on both normal and pathological immune factors in a variety of patients undergoing these procedures.
This multi-center study is an investigator-driven randomized controlled parallel group open-label clinical trial designed to evaluate the efficacy of addition of anti-IL-6 antibody tocilizumab (TCZ) to the standard of care (SOC) treatment as compared to the SOC alone in reducing the decline of graft function in kidney transplant recipients with chronic antibody-mediated rejection (cAMR). A total of 50 recipients will be allocated to receive either TCZ (n=25) added to the standard of care (SOC) or SOC alone (n=25) for a period of 24 months. Patients will be followed for an additional 12 months. Protocol kidney graft biopsies will be performed at 12 and 24 months. The primary outcome is the mean rate of change in graft function as assessed by estimated glomerular filtration rate (eGFR) slope from baseline to 24 months after start of treatment.
Kidney transplantation is the best therapy method for patients with uremia. The main factors affecting the long-term survival of the graft were chronic antibody-mediated rejection and the death of the patients. Newborn donor special antibody (DSA) is a major risk factor for chronic antibody-mediated rejection (AMR) and poor transplantation outcomes. Detection of mycophenolate mofetil (MMF) trough concentration can help estimate its exposure. Deficient exposure of MMF can lead to AMR after transplantation surgery. The aim of this study is to estimate the risk factors of one-year DSA after transplantation.
Chronic-active antibody-mediated rejection (cAMR) due to de novo or pre-formed donor specific antibody (DSA) is currently considered the main cause of long-term allograft losses.Based on the aim of reducing or eliminating DSA, some proposed different therapeutic regimens for cAMR treatment. All of these protocols were derived from previous experience using acute antibody-mediated rejection and desensitization protocols, and mainly consisted of steroids, plasma exchange (PE), IVIG and RTX in various modalities. More recently, bortezomib was also proposed.To evaluate the role of a therapeutic regimen with plasma exchange, intravenous immunoglobulins and rituximab with or without Bortezomib in chronic-active antibody-mediated rejection (cAMR) settings this study designed.
The diagnosis of AMR in lung transplant recipients is difficult and often comes too late, because of lack of standardized definition. The diagnosis is nowadays based on an expert multidisciplinary approach involving clinical, histopathological and immunological criteria. Hypothesis: the presence of intragraft donor specific antibodies (gDSAs) could be used as a new diagnostic tool for AMR in lung transplant recipients Study Objectives: to evaluate, in lung transplant patients with circulating DSAs, the diagnostic value of gDSAs in AMR and to analyze its prognostic value on graft outcome.
The aim is to compare the quantitative parameters of de novo anti-HLA DQ Donor Specific Antibodies (DSA), determined at the time of their discovery by surface plasmon resonance (SPR), between recipients that developed a Chronic Lung Allograft Dysfunction (CLAD) for the 2 years following DSA apparition and those who did not. If concentration, kinetics and/or affinity parameters of anti-DQ DSA are associated with CLAD development, new, non-invasive prognostic biomarkers of humoral rejection in lung transplantation will be discovered .
In France around 90,000 cases of end-stage chronic kidney disease patients treated either by dialysis (60%) or renal transplantation (just over 40%). In terms of patient survival and quality of life and also economic reasons, the goal in France is to increase renal transplantation instead of patients on dialysis. After renal transplant, two main causes of the graft loss after the first years are death of patient with functioning graft, and chronic AntiBody Mediated Rejection (ABMR). Double Filtration PlasmaPheresis (DFPP) has never been evaluated for this indication. DFPP makes it possible to treat larger volumes of plasma than plasma exchange, and essentially eliminates higher molecular weights molecules including immunoglobulins comprising DSA (donor-specific alloantibody) but also the C1q involved in the lesions of(ABMR). It is postulated that it will be more effective in treating ABMR than usual plasma exchanges. A chronic ABMR is the result of the appearance de novo production of anti-Human Leucocyte Antigen antibodies (HLA) against one or more graft antigens (DSA: donor-specific alloantibody).These DSAs will lead to accelerated arteriosclerosis in the graft vessels, which will result in rapidly progressive renal failure, usually associated with a high rate of proteinuria. Numerous studies have shown that up to 20% of renal transplant patients develop DSA within 5 years of renal transplantation. Today, no treatment has been shown to be effective in the case of chronic ABMR: the basis of treatment is the reduction/elimination of DSA ( by apheresis for example) and the prevention of its re-synthesis B lymphocytes/plasma cells of the patient (with rituximab for example). The investigators of this study propose in the context of the active ABMR demonstrated by renal biopsy to evaluate in combination with rituximab, a new apheresis technique double Plasma filtration (DFPP) instead of plasma Exchange.