Abatacept in B7-1-positive proteinuric kidney disease.
نویسندگان
چکیده
Abatacept (cytotoxic T-lymphocyte-associated antigen 4-immunoglobulin fusion protein [CTLA-4-Ig]) is a costimulatory inhibitor that targets B7-1 (CD80). The present report describes five patients who had focal segmental glomerulosclerosis (FSGS) (four with recurrent FSGS after transplantation and one with primary FSGS) and proteinuria with B7-1 immunostaining of podocytes in kidney-biopsy specimens. Abatacept induced partial or complete remissions of proteinuria in these patients, suggesting that B7-1 may be a useful biomarker for the treatment of some glomerulopathies. Our data indicate that abatacept may stabilize β1-integrin activation in podocytes and reduce proteinuria in patients with B7-1-positive glomerular disease.
منابع مشابه
Podocyte Expression of B7-1/CD80: Is it a Reliable Biomarker for the Treatment of Proteinuric Kidney Diseases with Abatacept?
The story of B7-1 (also known as CD80) and its possible association with nephrotic syndrome began with a chance observation that the gene for B7-1 is overexpressed in podocytes from mice deficient in the a3 integrin.1 The a3b1 integrin is an important adhesion receptor in podocytes and the deficient mice have abnormal podocytes and are proteinuric.2 The finding of B7-1 in podocytes was somewhat...
متن کاملInhibition of T-cell activation by the CTLA4-Fc Abatacept is sufficient to ameliorate proteinuric kidney disease.
Diabetic nephropathy (DN) remains an unmet medical challenge as its prevalence is projected to continue to increase and specific medicines for treatment remain undeveloped. Activation of the immune system, in particular T-cells, is emerging as a possible mechanism underlying DN disease progression in humans and animal models. We hypothesized that inhibition of T-cell activation will ameliorate ...
متن کاملAbatacept and Glomerular Diseases: The Open Road for the Second Signal as a New Target is Settled Down.
Glomerulopathy is the third most important cause of kidney disease. Proteinuria is the hallmark of glomerular damage, and a marker of progression of kidney disease, cardiovascular morbidity and mortality. Strategies to reduce proteinuria are partially successful, and despite proteinuria management, renal disease may still progress. Immunosuppression to treat glomerulopathies is nonspecific, par...
متن کاملUnsuccessful Treatment with Abatacept in Recurrent Focal Segmental Glomerulosclerosis after Kidney Transplantation
Recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation occurs in up to 20-50% of FSGS patients and is associated with inferior allograft survival. Treatment of both primary FSGS as well as recurrent FSGS after transplantation with plasma exchange and immunosuppression is often unsuccessful and remains a major challenge as the disease still leads to end-stage renal d...
متن کاملAbatacept Treatment Does Not Preserve Renal Function in the Streptozocin-Induced Model of Diabetic Nephropathy
Diabetic nephropathy (DN) is one of the most severe complications of diabetes and remains the largest cause of end-stage renal disease in the Western world. Treatment options are limited and novel therapies that effectively slow disease progression are warranted. Previous work suggested that treatment with CTLA4-Ig (abatacept), a molecule that binds and blocks B7-1 and is licensed for the treat...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- The New England journal of medicine
دوره 370 13 شماره
صفحات -
تاریخ انتشار 2013