Imperial College London
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DrCandiceRoufosse

Faculty of Medicine, Department of Immunology and Inflammation

Clinical Reader in Renal Pathology
 
 
 
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Contact

 

+44 (0)20 3313 3280c.roufosse

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Prendecki:2023:10.1002/art.42321,
author = {Prendecki, M and Gulati, K and Pisacano, N and Pinheiro, D and Bhatt, T and Mawhin, M-A and Toulza, F and Masuda, ES and Cowburn, A and Lodge, KM and Tam, FWK and Roufosse, C and Pusey, CD and McAdoo, SP},
doi = {10.1002/art.42321},
journal = {Arthritis and Rheumatology},
pages = {84--97},
title = {Syk activation in circulating and tissue innate immune cells in antineutrophil cytoplasmic antibody-associated vasculitis},
url = {http://dx.doi.org/10.1002/art.42321},
volume = {75},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - OBJECTIVE: Syk 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. METHODS: Phosphorylation 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. RESULTS: We 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. 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.
AU  - Prendecki,M
AU  - Gulati,K
AU  - Pisacano,N
AU  - Pinheiro,D
AU  - Bhatt,T
AU  - Mawhin,M-A
AU  - Toulza,F
AU  - Masuda,ES
AU  - Cowburn,A
AU  - Lodge,KM
AU  - Tam,FWK
AU  - Roufosse,C
AU  - Pusey,CD
AU  - McAdoo,SP
DO  - 10.1002/art.42321
EP  - 97
PY  - 2023///
SN  - 2326-5205
SP  - 84
TI  - Syk activation in circulating and tissue innate immune cells in antineutrophil cytoplasmic antibody-associated vasculitis
T2  - Arthritis and Rheumatology
UR  - http://dx.doi.org/10.1002/art.42321
UR  - https://www.ncbi.nlm.nih.gov/pubmed/36428281
UR  - https://onlinelibrary.wiley.com/doi/10.1002/art.42321
UR  - http://hdl.handle.net/10044/1/100887
VL  - 75
ER  -
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