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The purpose of this study is to determine if administration of rituximab blocks the development of donor specific antibodies (DSA) in transplant recipients who have developed renal dysfunction and DSA after renal transplant. It is hoped that by blocking DSA production renal function will stabilize or improve.
A long established risk factor for late renal allograft loss is the development of DSA. Recent studies from our group and others have shown that these antibodies are probably responsible for chronic rejection by attacking the vascular endothelium and fixing complement (detected as C4d in renal biopsies). Studies in humans and monkeys have shown that circulating antibody and complement deposition precede the development of chronic graft injury. Interruption of antibody production is a potential beneficial strategy to prevent late graft loss from this mechanism.
Therapeutic regimens that have been used in an attempt to deplete HLA or ABO antibodies include plasmapheresis, IVIg, tacrolimus and mycophenolate mofetil (MMF), and anti-CD20 (rituximab). Of these regimens, the most specific is anti-CD20, rituximab (rituxan), a therapy now FDA approved for B cell proliferative diseases. Although initially introduced for the treatment of neoplasm, the humoral immunosuppressant effects of rituximab have been shown to have clinical significance. Rituximab interferes with both primary and secondary humoral responses by eliminating B-cells prior to antigen exposure, thus interfering with differentiation into antibody secreting cells and specific antibody production.
Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Massachusetts General Hospital
Published on BioPortfolio: 2014-08-27T03:47:18-0400
Our standard immunosuppressive treatment after renal transplantation is a combination of tacrolimus, mycophenolate mofetil, and prednisolone. With this regimen the incidence of acute rejec...
Acute kidney allograft rejection is the major cause for a loss of graft function and has a negative impact on long-term graft survival. Anti-rejection therapy traditionally focuses on T ce...
The purpose of this research is to discover the different patterns of cytokine production in patients who may develop Bronchiolitis Obliterans Syndrome-0p (BOS-0p) which means ongoing reje...
Rituximab (a monoclonal antibody raised against CD20) is used to treat various immune disorders. In some cases such as treatment of humoral acute rejection of renal transplant, thrombotic ...
About one third of prospective kidney transplant recipients have antibodies in their blood directed against the tissues of their only available kidney donor. Recently, "desensitisation" tr...
Chronic rejection of transplanted organs is a major obstacle in organ transplantation. The main symptoms of chronic rejection are vessel occlusion and tissue fibrosis. Macrophages play a crucial role ...
PALG CLL4 is the first, randomized, phase IIIb study with cladribine, cyclophosphamide and rituximab (RCC) induction and subsequent maintenance with rituximab in previously untreated chronic lymphocyt...
Chronic rejection is the Achilles' heel of modern lung transplantation, characterized by a slow, progressive decline in allograft function. Clinically, this manifests as obstructive disease, restricti...
Rituximab maintenance versus observation following abbreviated induction with chemoimmunotherapy in elderly patients with previously untreated chronic lymphocytic leukaemia (CLL 2007 SA): an open-label, randomised phase 3 study.
Most patients with chronic lymphocytic leukaemia relapse after initial therapy combining chemotherapy with rituximab. We assessed the efficacy and safety of rituximab maintenance treatment versus obse...
Chronic active antibody-mediated rejection (caAMR) is a major cause of allograft loss after kidney transplantation (1). The BANFF 2013 classification redefined caAMR by the presence of donor-specific ...
Non-acceptance, negative attitudes, hostility or excessive criticism of the individual which may precipitate feelings of rejection.
A murine-derived monoclonal antibody and ANTINEOPLASTIC AGENT that binds specifically to the CD20 ANTIGEN and is used in the treatment of LEUKEMIA; LYMPHOMA and RHEUMATOID ARTHRITIS.
A general term for the complex phenomena involved in allo- and xenograft rejection by a host and graft vs host reaction. Although the reactions involved in transplantation immunology are primarily thymus-dependent phenomena of cellular immunity, humoral factors also play a part in late rejection.
A subcategory of CHRONIC OBSTRUCTIVE PULMONARY DISEASE. The disease is characterized by hypersecretion of mucus accompanied by a chronic (more than 3 months in 2 consecutive years) productive cough. Infectious agents are a major cause of chronic bronchitis.
A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA.
Organ transplantation is the moving of an organ from one body to another or from a donor site to another location on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative ...
Nephrology - kidney function
Nephrology is a specialty of medicine and pediatrics that concerns itself with the study of normal kidney function, kidney problems, the treatment of kidney problems and renal replacement therapy (dialysis and kidney transplantation). Systemic conditions...