An inhibitor of spleen tyrosine kinase suppresses experimental crescentic glomerulonephritis

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A spleen tyrosine kinase inhibitor reduces the severity of established glomerulonephritis.

Antibody-mediated glomerulonephritis, including that resulting from immune complexes, is an important cause of renal failure and is in need of more specific and effective treatment. Binding of antibody or immune complexes to Fc receptors activates intracellular signal transduction pathways, including spleen tyrosine kinase (Syk), leading to the production of inflammatory cytokines. We examined ...

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An Oral Spleen Tyrosine Kinase (Syk) Inhibitor for Rheumatoid Arthritis

From the Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital and Harvard Medical School, Boston (M.E.W.); Division of Rheumatology, University of California at San Diego, San Diego (A.K.); Division of Rheumatology, Stanford University, Palo Alto, CA (M.G.); and Rigel, South San Francisco, CA (T.K.M., E.B.G., D.B.M.). Address reprint requests to Dr. Weinblatt at the D...

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Targeting Spleen Tyrosine Kinase-Bruton's Tyrosine Kinase Axis for Immunologically Mediated Glomerulonephritis

The importance of B-cell activation and immune complex-mediated Fc-receptor activation in the pathogenesis of immunologically mediated glomerulonephritis has long been recognized. The two nonreceptor tyrosine kinases, spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (Btk), are primarily expressed by hematopoietic cells, and participate in B-cell-receptor- and Fc-receptor-mediated activ...

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Spleen tyrosine kinase (Syk) inhibitor for rheumatoid arthritis.

BACKGROUND Spleen tyrosine kinase (Syk) is an important modulator of immune signaling. The objective of this phase 2 study was to evaluate the efficacy and safety of R788, an oral inhibitor of Syk, in patients with active rheumatoid arthritis despite methotrexate therapy. METHODS We enrolled 457 patients who had active rheumatoid arthritis despite long-term methotrexate therapy in a 6-month, ...

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Plasminogen activator inhibitor-1 is a significant determinant of renal injury in experimental crescentic glomerulonephritis.

Crescentic glomerulonephritis is characterized by glomerular fibrin deposition, and experimental crescentic glomerulonephritis has been shown to be fibrin-dependent. Net fibrin deposition is a balance between activation of the coagulation system causing glomerular fibrin deposition and fibrin removal by the plasminogen-plasmin (fibrinolytic) system. Plasminogen activator inhibitor-1 (PAI-1) inh...

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ژورنال

عنوان ژورنال: International Journal of Immunopathology and Pharmacology

سال: 2018

ISSN: 2058-7384,2058-7384

DOI: 10.1177/2058738418783404