Vasculitis & polymyalgia rheumatica
Syk Activation in Circulating and Tissue Innate Immune Cells in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Authors' conclusion
These 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.
Study context
- Population
- Healthy controls and ANCA-associated vasculitis (AAV) patients; myeloid cells and tissue at sites of inflammation
- Comparison
- Active AAV vs AAV in remission vs healthy controls; Syk inhibition vs none in MPO-ANCA IgG-stimulated cells
Methodological detailsflow cytometry, functional assays, NanoString targeted gene analysis, immunohistochemistry, RNAscope in situ hybridization
- Flow cytometry
- Functional assays
- NanoString targeted gene analysis
- Immunohistochemistry
- RNAscope in situ hybridization
Main finding
As reported in the abstract
- Increased phosphorylated Syk at critical activatory tyrosine residues in blood neutrophils and monocytes in active AAV vs remission or healthy controls
- Syk phosphorylated in vitro after MPO-ANCA IgG stimulation; Syk inhibition prevented antineutrophil cytoplasm antibody (ANCA)-mediated cellular responses
- Up-regulation of Fc receptors (FcR)- and Syk-dependent signaling pathways after MPO-ANCA IgG stimulation
- Syk expressed and phosphorylated in tissue leukocytes at sites of organ inflammation in AAV
Original publication
Syk Activation in Circulating and Tissue Innate Immune Cells in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis. Arthritis Rheumatol. Published 25 November 2022. doi:10.
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