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The complement system as a potential therapeutic target in rheumatic disease

Trouw, Leendert A.; Pickering, Matthew C. and Blom, Anna M. LU (2017) In Nature Reviews Rheumatology 13(9). p.538-547
Abstract

Complement activation is associated with common rheumatic diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and systemic vasculitis. Evidence linking complement activation to these diseases includes the presence of complement deposition in affected tissues, decreased levels of complement proteins and high levels of complement activation fragments in the blood and/or synovial fluid of patients with these diseases, as well as data from experimental models. Eculizumab, a monoclonal antibody that inhibits the complement component C5, is now approved for the treatment of rare conditions involving complement hyperactivation, and the success of this therapy has renewed interest in understanding the utility of... (More)

Complement activation is associated with common rheumatic diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and systemic vasculitis. Evidence linking complement activation to these diseases includes the presence of complement deposition in affected tissues, decreased levels of complement proteins and high levels of complement activation fragments in the blood and/or synovial fluid of patients with these diseases, as well as data from experimental models. Eculizumab, a monoclonal antibody that inhibits the complement component C5, is now approved for the treatment of rare conditions involving complement hyperactivation, and the success of this therapy has renewed interest in understanding the utility of complement inhibition in rheumatological practice, particularly for SLE. For example, inhibiting C5 is a potential means of reducing glomerular inflammation in lupus nephritis or treating thrombotic microangiopathy in SLE. The complement system is one of multiple mediators of tissue injury in complex diseases such as SLE, and identifying the disease context in which complement activation has a predominant role is a challenge. An added difficulty in RA is identifying a role for therapeutic complement inhibition within the diverse treatment modalities already available. In this Review, evidence for the therapeutic potential of complement manipulation in rheumatology practice is evaluated.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
rheumatic disease, complement system, therapeutic target
in
Nature Reviews Rheumatology
volume
13
issue
9
pages
10 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85028014367
  • pmid:28794515
  • wos:000408122600015
ISSN
1759-4790
DOI
10.1038/nrrheum.2017.125
language
English
LU publication?
yes
id
292dedf4-364c-4586-b543-94f75957f8cb
date added to LUP
2017-09-01 14:19:56
date last changed
2017-09-18 11:43:58
@article{292dedf4-364c-4586-b543-94f75957f8cb,
  abstract     = {<p>Complement activation is associated with common rheumatic diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and systemic vasculitis. Evidence linking complement activation to these diseases includes the presence of complement deposition in affected tissues, decreased levels of complement proteins and high levels of complement activation fragments in the blood and/or synovial fluid of patients with these diseases, as well as data from experimental models. Eculizumab, a monoclonal antibody that inhibits the complement component C5, is now approved for the treatment of rare conditions involving complement hyperactivation, and the success of this therapy has renewed interest in understanding the utility of complement inhibition in rheumatological practice, particularly for SLE. For example, inhibiting C5 is a potential means of reducing glomerular inflammation in lupus nephritis or treating thrombotic microangiopathy in SLE. The complement system is one of multiple mediators of tissue injury in complex diseases such as SLE, and identifying the disease context in which complement activation has a predominant role is a challenge. An added difficulty in RA is identifying a role for therapeutic complement inhibition within the diverse treatment modalities already available. In this Review, evidence for the therapeutic potential of complement manipulation in rheumatology practice is evaluated.</p>},
  author       = {Trouw, Leendert A. and Pickering, Matthew C. and Blom, Anna M.},
  issn         = {1759-4790},
  keyword      = {rheumatic disease,complement system,therapeutic target},
  language     = {eng},
  month        = {09},
  number       = {9},
  pages        = {538--547},
  publisher    = {Nature Publishing Group},
  series       = {Nature Reviews Rheumatology},
  title        = {The complement system as a potential therapeutic target in rheumatic disease},
  url          = {http://dx.doi.org/10.1038/nrrheum.2017.125},
  volume       = {13},
  year         = {2017},
}