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Rheumatoid arthritis and the complement system

Okroj, Marcin LU ; Heinegård, Dick LU ; Holmdahl, Rikard LU and Blom, Anna LU (2007) In Annals of Medicine 39(7). p.517-530
Abstract
Complement activation contributes to a pathological process in a number of autoimmune and inflammatory diseases, including rheumatoid arthritis (RA). In this review we summarize current knowledge of complement contribution to RA, based on clinical observations in patients and in vivo animal models, as well as on experiments in vitro aiming at elucidation of underlying molecular mechanisms. There is strong evidence that both the classical and the alternative pathways of complement are pathologically activated during RA as well as in animal models for RA. The classical pathway can be initiated by several triggers present in the inflamed joint such as deposited autoantibodies, dying cells, and exposed cartilage proteins such as fibromodulin.... (More)
Complement activation contributes to a pathological process in a number of autoimmune and inflammatory diseases, including rheumatoid arthritis (RA). In this review we summarize current knowledge of complement contribution to RA, based on clinical observations in patients and in vivo animal models, as well as on experiments in vitro aiming at elucidation of underlying molecular mechanisms. There is strong evidence that both the classical and the alternative pathways of complement are pathologically activated during RA as well as in animal models for RA. The classical pathway can be initiated by several triggers present in the inflamed joint such as deposited autoantibodies, dying cells, and exposed cartilage proteins such as fibromodulin. B cells producing autoantibodies, which in turn form immune complexes, contribute to RA pathogenesis partly via activation of complement. It appears that anaphylatoxin C5a is the main product of complement activation responsible for tissue damage in RA although deposition of membrane attack complex as well as opsonization with fragments of C3b are also important. Success of complement inhibition in the experimental models described so far encourages novel therapeutic approaches to the treatment of human RA. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Annals of Medicine
volume
39
issue
7
pages
517 - 530
publisher
Informa Healthcare
external identifiers
  • pmid:17852027
  • wos:000251046500003
  • scopus:35649005450
ISSN
1365-2060
DOI
10.1080/07853890701477546
language
English
LU publication?
yes
id
f2a65310-a93b-456a-88b6-bd903f6db015 (old id 1137891)
date added to LUP
2008-08-15 15:46:19
date last changed
2017-11-05 04:44:49
@article{f2a65310-a93b-456a-88b6-bd903f6db015,
  abstract     = {Complement activation contributes to a pathological process in a number of autoimmune and inflammatory diseases, including rheumatoid arthritis (RA). In this review we summarize current knowledge of complement contribution to RA, based on clinical observations in patients and in vivo animal models, as well as on experiments in vitro aiming at elucidation of underlying molecular mechanisms. There is strong evidence that both the classical and the alternative pathways of complement are pathologically activated during RA as well as in animal models for RA. The classical pathway can be initiated by several triggers present in the inflamed joint such as deposited autoantibodies, dying cells, and exposed cartilage proteins such as fibromodulin. B cells producing autoantibodies, which in turn form immune complexes, contribute to RA pathogenesis partly via activation of complement. It appears that anaphylatoxin C5a is the main product of complement activation responsible for tissue damage in RA although deposition of membrane attack complex as well as opsonization with fragments of C3b are also important. Success of complement inhibition in the experimental models described so far encourages novel therapeutic approaches to the treatment of human RA.},
  author       = {Okroj, Marcin and Heinegård, Dick and Holmdahl, Rikard and Blom, Anna},
  issn         = {1365-2060},
  language     = {eng},
  number       = {7},
  pages        = {517--530},
  publisher    = {Informa Healthcare},
  series       = {Annals of Medicine},
  title        = {Rheumatoid arthritis and the complement system},
  url          = {http://dx.doi.org/10.1080/07853890701477546},
  volume       = {39},
  year         = {2007},
}