ArticleJournal of the American Society of Nephrology : JASN2014
Spleen tyrosine kinase inhibition attenuates autoantibody production and reverses experimental autoimmune GN.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 55 citations in OpenAlex.
- Sustained response off-treatment and thrombotic events in patients with immune thrombocytopenia treated with fostamatinib: a systematic review and meta-analysis.Haematologica · 2026Article
- The Src-Family Kinases Hck, Fgr and Lyn Drive Immune Complex-Mediated Glomerulonephritis Through the Syk Tyrosine Kinase.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Targeting B Cells and Plasma Cells in Glomerular Disease.Journal of the American Society of Nephrology : JASN · 2025Review
- Clinical advances in immunotherapy for immune-mediated glomerular diseases.Clinical and experimental medicine · 2023Review
- Syk Activation in Circulating and Tissue Innate Immune Cells in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- Inhibition of spleen tyrosine kinase decreases donor specific antibody levels in a rat model of sensitization.Scientific reports · 2022Article
- Kinase inhibitors developed for treatment of hematologic malignancies: implications for immune modulation in COVID-19.Blood advances · 2021Review
- Acute Kidney Injury Induced Lupus Exacerbation Through the Enhanced Neutrophil Extracellular Traps (and Apoptosis) in Fcgr2b Deficient Lupus Mice With Renal Ischemia Reperfusion Injury.Frontiers in immunology · 2021Article
- A High-Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury.Cell reports. Medicine · 2020Article
- A High Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury during the COVID-19 pandemic.bioRxiv : the preprint server for biology · 2020Article
- Spleen tyrosine kinase inhibition is an effective treatment for established vasculitis in a pre-clinical model.Kidney international · 2020Article
- Role of spleen tyrosine kinase in liver diseases.World journal of gastroenterology · 2020Review
- A Modified Peptide Derived from Goodpasture Autoantigen Arrested and Attenuated Kidney Injuries in a Rat Model of Anti-GBM Glomerulonephritis.Journal of the American Society of Nephrology : JASN · 2020Article
- Syk Inhibitor Attenuates Polymicrobial Sepsis in FcgRIIb-Deficient Lupus Mouse Model, the Impact of Lupus Characteristics in Sepsis.Journal of innate immunity · 2020Article
- Perspectives on how mucosal immune responses, infections and gut microbiome shape IgA nephropathy and future therapies.Theranostics · 2020Review
- Macrophages: versatile players in renal inflammation and fibrosis.Nature reviews. Nephrology · 2019Review
- Role of the Spleen Tyrosine Kinase Pathway in Driving Inflammation in IgA Nephropathy.Seminars in nephrology · 2018Review
- Antineutrophil cytoplasmic antibody associated vasculitides with renal involvement: Open challenges in the remission induction therapy.World journal of nephrology · 2018Review
- New insights into the pathogenesis of IgA nephropathy.Pediatric nephrology (Berlin, Germany) · 2018Review
- Primary IgA nephropathy: current challenges and future prospects.International journal of nephrology and renovascular disease · 2018Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Spleen tyrosine kinase (SYK) has an important role in immunoreceptor signaling, and SYK inhibition has accordingly attenuated immune-mediated injury in several in vivo models. However, the effect of SYK inhibition on autoantibody production remains unclear, and SYK inhibition has not been studied in an autoimmune model of renal disease. We, therefore, studied the effect of SYK inhibition in experimental autoimmune GN, a rodent model of antiglomerular basement membrane disease. We show glomerular SYK expression and activation by immunohistochemistry in both experimental and clinical disease, and we show that treatment with fostamatinib, a small molecule kinase inhibitor selective for SYK, completely prevents the induction of experimental autoimmune GN. In established experimental disease, introduction of fostamatinib treatment led to cessation of autoantibody production, reversal of renal injury, preservation of biochemical renal function, and complete protection from lung hemorrhage. B cell ELISpot and flow cytometric analysis suggest that short-term fostamatinib treatment inhibits the generation and activity of antigen-specific B cells without affecting overall B-cell survival. Additionally, fostamatinib inhibited proinflammatory cytokine production by nephritic glomeruli ex vivo and cultured bone marrow-derived macrophages in vitro, suggesting additional therapeutic effects independent of effects on autoantibody production that are likely related to inhibited Fc receptor signaling within macrophages in diseased glomeruli. Given these encouraging results in an in vivo model that is highly applicable to human disease, we believe clinical studies targeting SYK in GN are now warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.