Imperial College London
Alternate

PROFESSOR H. TERENCE COOK

Faculty of Medicine, Department of Immunology and Inflammation

Emeritus Professor
 
 
 
//

Contact

 

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

 
 
//

Assistant

 

Miss Claudia Rocchi +44 (0)20 3313 2315

 
//

Location

 

9N9Commonwealth BuildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Gilmore:2021:10.1016/j.kint.2020.09.028,
author = {Gilmore, AC and Zhang, Y and Cook, HT and Lavin, DP and Katti, S and Wang, Y and Johnson, KK and Kim, S and Pickering, MC},
doi = {10.1016/j.kint.2020.09.028},
journal = {Kidney International},
pages = {396--404},
title = {Complement activity is regulated in C3 glomerulopathy by IgG-factor H fusion proteins with and without properdin targeting domains},
url = {http://dx.doi.org/10.1016/j.kint.2020.09.028},
volume = {99},
year = {2021}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - C3 glomerulopathy is characterized by accumulation of complement C3 within glomeruli. Causes include, but are not limited to, abnormalities in factor H, the major negative regulator of the complement alternative pathway. Factor H-deficient (Cfh-/-) mice develop C3 glomerulopathy together with a reduction in plasma C3 levels. Using this model, we assessed the efficacy of two fusion proteins containing the factor H alternative pathway regulatory domains (FH1-5) linked to either a non-targeting mouse immunoglobulin (IgG-FH1-5) or to an anti-mouse properdin antibody (Anti-P-FH1-5). Both proteins increased plasma C3 and reduced glomerular C3 deposition to an equivalent extent, suggesting that properdin-targeting was not required for FH1-5 to alter C3 activation in either plasma or glomeruli. Following IgG-FH1-5 administration, plasma C3 levels temporally correlated with changes in factor B levels whereas plasma C5 levels correlated with changes in plasma properdin levels. Notably, the increases in plasma C5 and properdin levels persisted for longer than the increases in C3 and factor B. In Cfh-/- mice IgG-FH1-5 reduced kidney injury during accelerated serum nephrotoxic nephritis. Thus, our data demonstrate that IgG-FH1-5 restored circulating alternative pathway activity and reduced glomerular C3 deposition in Cfh-/- mice and that plasma properdin levels are a sensitive marker of C5 convertase activity in factor H deficiency. The immunoglobulin conjugated FH1-5 protein, through its comparatively long plasma half-life, may be a potential therapy for C3 glomerulopathy.
AU  - Gilmore,AC
AU  - Zhang,Y
AU  - Cook,HT
AU  - Lavin,DP
AU  - Katti,S
AU  - Wang,Y
AU  - Johnson,KK
AU  - Kim,S
AU  - Pickering,MC
DO  - 10.1016/j.kint.2020.09.028
EP  - 404
PY  - 2021///
SN  - 0085-2538
SP  - 396
TI  - Complement activity is regulated in C3 glomerulopathy by IgG-factor H fusion proteins with and without properdin targeting domains
T2  - Kidney International
UR  - http://dx.doi.org/10.1016/j.kint.2020.09.028
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33129896
UR  - http://hdl.handle.net/10044/1/87143
VL  - 99
ER  -
Download