ArticleArthritis & rheumatology (Hoboken, N.J.)2023
Syk Activation in Circulating and Tissue Innate Immune Cells in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- 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
- BAFF and APRIL signaling in the B-cell lineage: implications for the pathogenesis of ANCA-associated vasculitis.Frontiers in immunology · 2026Review
- Fostamatinib (R788), a spleen tyrosine kinase inhibitor, sensitizes pancreatic cancer cells to oncolytic vesicular stomatitis virus.Molecular therapy. Oncology · 2025Article
- Novel SYK Variant Causes Enhanced SYK Autophosphorylation and PI3K Activation in an Antibody-Deficient Patient.Journal of clinical immunology · 2025Article
- NLRP3 inflammasome activity and pyroptosis are involved in CD206Acta biochimica et biophysica Sinica · 2025Article
- Neutrophils and Platelets as Key Players in the Pathogenesis of ANCA-Associated Vasculitis and Potential Sources of Disease Activity Biomarkers.Diagnostics (Basel, Switzerland) · 2025Review
- Advances in the treatment of ANCA-associated vasculitis.Nature reviews. Rheumatology · 2025Review
- Bruton's tyrosine kinase is a possible therapeutic target in microscopic polyangiitis.Arthritis research & therapy · 2023Article
- Spleen tyrosine kinase (SYK) signals are implicated in cardio-cerebrovascular diseases.Heliyon · 2023Review
- Analysis of intracellular tyrosine phosphorylation in circulating neutrophils as a rapid assay for theFrontiers in pharmacology · 2023Article
- The involvement of NETs in ANCA-associated vasculitis.Frontiers in immunology · 2023Review
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveSyk is a cytoplasmic protein tyrosine kinase that plays a role in signaling via B cell and Fc receptors (FcR). FcR engagement and signaling via Syk is thought to be important in antineutrophil cytoplasm antibody (ANCA) IgG-mediated neutrophil activation. This study was undertaken to investigate the role of Syk in ANCA-induced myeloid cell activation and vasculitis pathogenesis.
methodsPhosphorylation of Syk in myeloid cells from healthy controls and ANCA-associated vasculitis (AAV) patients was analyzed using flow cytometry. The effect of Syk inhibition on myeloperoxidase (MPO)-ANCA IgG activation of cells was investigated using functional assays (interleukin-8 and reactive oxygen species production) and targeted gene analysis with NanoString. Total and phosphorylated Syk at sites of tissue inflammation in patients with AAV was assessed using immunohistochemistry and RNAscope in situ hybridization.
resultsWe identified increased phosphorylated Syk at critical activatory tyrosine residues in blood neutrophils and monocytes from patients with active AAV compared to patients with disease in remission or healthy controls. Syk was phosphorylated in vitro following MPO-ANCA IgG stimulation, and Syk inhibition was able to prevent ANCA-mediated cellular responses. Using targeted gene expression analysis, we identified up-regulation of FcR- and Syk-dependent signaling pathways following MPO-ANCA IgG stimulation. Finally, we showed that Syk is expressed and phosphorylated in tissue leukocytes at sites of organ inflammation in AAV.
conclusionThese findings indicate that Syk plays a critical role in MPO-ANCA IgG-induced myeloid cell responses and that Syk is activated in circulating immune cells and tissue immune cells in AAV; therefore, Syk inhibition may be a potential therapeutic option.
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