Imperial College London
Alternate

ProfessorMatthewPickering

Faculty of Medicine, Department of Immunology and Inflammation

Centre Director, Professor of Rheumatology
 
 
 
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Contact

 

matthew.pickering Website

 
 
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Assistant

 

Miss Claudia Rocchi +44 (0)20 3313 2315

 
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Location

 

9N12Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lou:2020:10.1038/s41419-020-02928-6,
author = {Lou, H and Wojciak-Stothard, B and Ruseva, MM and Cook, HT and Kelleher, P and Pickering, MC and Mongkolsapaya, J and Screaton, GR and Xu, X-N},
doi = {10.1038/s41419-020-02928-6},
journal = {Cell Death and Disease},
title = {Autoantibody-dependent amplification of inflammation in SLE},
url = {http://dx.doi.org/10.1038/s41419-020-02928-6},
volume = {11},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Anti-double stranded DNA antibodies (anti-dsDNA) are a hallmark of SLE but their role in disease pathogenesis is not fully resolved. Anti-dsDNA in serum are highly heterogeneous therefore in this study, we aimed to dissect the functional specificities of anti-dsDNA using a panel of human monoclonal antibodies (humAbs) generated from patients with active lupus nephritis. A total of 46 ANA reactive humAbs were isolated and divided into four broad classes based on their reactivity to histones, DNA and Crithidia. Functional analysis indicated that one subclass of antibodies bound strongly to decondensed DNA areas in neutrophil extracellular traps (NETs) and protected NETs from nuclease digestion, similar to the sera from active SLE patients. In addition, these anti-dsDNA antibodies could stimulate type I interferon responses in mononuclear phagocytic cells, or NF-kB activity in endothelial cells, by uptake of NETs-anti-NETs immune complexes and subsequently trigging inflammatory responses in an Fc-gamma receptor (Fcg-R)-dependant manner. Together our data suggest that only a subset of anti-dsDNA antibodies is capable to amplify inflammatory responses by deposit in the nephritic kidney in vivo, protecting NETs digestion as well as uptake of NETs immune complexes into Fcg-R-expressing cells in vitro.
AU  - Lou,H
AU  - Wojciak-Stothard,B
AU  - Ruseva,MM
AU  - Cook,HT
AU  - Kelleher,P
AU  - Pickering,MC
AU  - Mongkolsapaya,J
AU  - Screaton,GR
AU  - Xu,X-N
DO  - 10.1038/s41419-020-02928-6
PY  - 2020///
SN  - 2041-4889
TI  - Autoantibody-dependent amplification of inflammation in SLE
T2  - Cell Death and Disease
UR  - http://dx.doi.org/10.1038/s41419-020-02928-6
UR  - http://hdl.handle.net/10044/1/82665
VL  - 11
ER  -
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