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Abatacept in B7-1-positive proteinuric kidney disease.
N. Engl. J. Med..Dec 19, 2013;369(25):2416-23.
Yu CC, Fornoni A, Weins A, Hakroush S, Maiguel D, Sageshima J, Chen L, Ciancio G, Faridi MH, Behr D, Campbell KN, Chang JM, Chen HC, Oh J, Faul C, Arnaout MA, Fiorina P, Gupta V, Greka A, Burke GW, Mundel P.
From the Department of Medicine, Massachusetts General Hospital and Harvard Medical School (C.-C.Y., A.W., S.H., D.B., M.A.A., A.G., P.M.), Department of Pathology, Brigham and Women's Hospital and Harvard Medical School (A.W.), and Division of Nephrology, Children's Hospital Boston (P.F.) - all in Boston; the Graduate Institute of Medicine, College of Medicine (C.-C.Y.), and Department of Internal Medicine (J.-M.C., H.-C.C.), Kaohsiung Medical University, Kaohsiung, Taiwan; the Division of Nephrology and Hypertension (A.F., D.M., M.H.F., C.F., V.G.) and Lilian Jean Kaplan Division of Kidney-Pancreas Transplantation, Miami Transplant Institute, Department of Surgery (J.S., L.C., G.C., G.W.B.), University of Miami Miller School of Medicine, Miami; the Division of Nephrology, Mount Sinai School of Medicine, New York (K.N.C.); and Pediatric Nephrology, Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (J.O.).
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.