Imperial College London
Alternate

PROFESSOR H. TERENCE COOK

Faculty of Medicine, Department of Immunology and Inflammation

Emeritus Professor
 
 
 
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Contact

 

+44 (0)20 3313 2009t.h.cook

 
 
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Assistant

 

Miss Claudia Rocchi +44 (0)20 3313 2315

 
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Location

 

9N9Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Tempest-Roe:2022:10.1038/s41598-022-06413-2,
author = {Tempest-Roe, S and Prendecki, M and McAdoo, S and Tanna, A and Turner-Stokes, T and Masuda, E and Willicombe, M and Cook, T and Roufosse, C and Taube, D and Pusey, C and Tam, F},
doi = {10.1038/s41598-022-06413-2},
journal = {Scientific Reports},
title = {Inhibition of spleen tyrosine kinase decreases donor specific antibody levels in a rat model of sensitization},
url = {http://dx.doi.org/10.1038/s41598-022-06413-2},
volume = {12},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Antibody mediated rejection is a major cause of renal allograft loss. Circulating preformed donor specific antibodies (DSA) can result as a consequence of blood transfusion, pregnancy or prior transplantation. Current treatment strategies are limited due to partial or transient efficacy, adverse side-effects or patient unsuitability. Previous in vivo studies exploring autoimmune diseases have shown that spleen tyrosine kinase (SYK) signalling is involved in the development of pathogenic autoantibody. The role of SYK in allogenic antibody production is unknown, and we investigated this in a rodent model of sensitization, established by the transfusion of F344 whole blood into LEW rats. Two-week treatment of sensitized rats with selective SYK inhibitor fostamatinib strongly blocked circulating DSA production without affecting overall total immunoglobulin levels, and inhibition was sustained up to 5 weeks post-completion of the treatment regimen. Fostamatinib treatment did not affect mature B cell subset or plasma cell levels, which remained similar between non-treated controls, vehicle treated and fostamatinib treated animals. Our data indicate fostamatinib may provide an alternative therapeutic option for patients who are at risk of sensitization following blood transfusion while awaiting renal transplant.
AU  - Tempest-Roe,S
AU  - Prendecki,M
AU  - McAdoo,S
AU  - Tanna,A
AU  - Turner-Stokes,T
AU  - Masuda,E
AU  - Willicombe,M
AU  - Cook,T
AU  - Roufosse,C
AU  - Taube,D
AU  - Pusey,C
AU  - Tam,F
DO  - 10.1038/s41598-022-06413-2
PY  - 2022///
SN  - 2045-2322
TI  - Inhibition of spleen tyrosine kinase decreases donor specific antibody levels in a rat model of sensitization
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-022-06413-2
UR  - http://hdl.handle.net/10044/1/93054
VL  - 12
ER  -
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