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C4b-binding protein (C4BP) inhibits development of experimental arthritis in mice.

Blom, Anna LU orcid ; Nandakumar, Kutty S and Holmdahl, Rikard LU (2009) In Annals of the Rheumatic Diseases 68. p.136-142
Abstract
OBJECTIVES: To assess the human complement inhibitor C4b-binding protein (C4BP) for treatment of arthritis. METHODS: We have used two mouse models of rheumatoid arthritis (RA) to assess the therapeutic effect of C4BP on different phases of arthritis, the collagen antibody induced arthritis (CAIA), an acute antibody induced disease and the collagen induced arthritis (CIA), which carries the full complexity of arthritis. RESULTS: Purified human C4BP injected intraperitoneally alleviated CAIA significantly in a manner similar to cobra venom factor that depletes complement due to massive activation. Furthermore, C4BP was injected before and after the disease development into CIA mice. In the former case, the disease onset was delayed and in... (More)
OBJECTIVES: To assess the human complement inhibitor C4b-binding protein (C4BP) for treatment of arthritis. METHODS: We have used two mouse models of rheumatoid arthritis (RA) to assess the therapeutic effect of C4BP on different phases of arthritis, the collagen antibody induced arthritis (CAIA), an acute antibody induced disease and the collagen induced arthritis (CIA), which carries the full complexity of arthritis. RESULTS: Purified human C4BP injected intraperitoneally alleviated CAIA significantly in a manner similar to cobra venom factor that depletes complement due to massive activation. Furthermore, C4BP was injected before and after the disease development into CIA mice. In the former case, the disease onset was delayed and in the latter, the severity of the disease was reduced in animals treated with C4BP. However, C4BP did not affect the anti-CII antibody synthesis. C4BP present in mouse sera decreased activity of the classical but not the alternative pathway of the complement system when these were assessed in a fluid phase. However, C4BP was efficiently inhibiting the alternative pathway when present on the activating surface. Taken together, the disease ameliorating effect of C4BP appears to be related to inhibition of both pathways of complement. CONCLUSIONS: Although human C4BP was cleared relatively fast from the circulation and was only moderately affecting complement activity, its effect on the disease severity was substantial, suggesting that minor alterations in complement activity can have significant therapeutic value in RA. (Less)
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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Annals of the Rheumatic Diseases
volume
68
pages
136 - 142
publisher
BMJ Publishing Group
external identifiers
  • pmid:18276745
  • wos:000261755800024
  • scopus:58349122882
  • pmid:18276745
ISSN
1468-2060
DOI
10.1136/ard.2007.085753
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Inflammation Research (013212019), Clinical Chemistry, Malmö (013016000), Protein Chemistry (013017510)
id
b08967e4-98c2-4fda-88a7-2b1e99a0614a (old id 1041920)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18276745?dopt=Abstract
date added to LUP
2016-04-04 09:08:09
date last changed
2022-05-16 23:00:45
@article{b08967e4-98c2-4fda-88a7-2b1e99a0614a,
  abstract     = {{OBJECTIVES: To assess the human complement inhibitor C4b-binding protein (C4BP) for treatment of arthritis. METHODS: We have used two mouse models of rheumatoid arthritis (RA) to assess the therapeutic effect of C4BP on different phases of arthritis, the collagen antibody induced arthritis (CAIA), an acute antibody induced disease and the collagen induced arthritis (CIA), which carries the full complexity of arthritis. RESULTS: Purified human C4BP injected intraperitoneally alleviated CAIA significantly in a manner similar to cobra venom factor that depletes complement due to massive activation. Furthermore, C4BP was injected before and after the disease development into CIA mice. In the former case, the disease onset was delayed and in the latter, the severity of the disease was reduced in animals treated with C4BP. However, C4BP did not affect the anti-CII antibody synthesis. C4BP present in mouse sera decreased activity of the classical but not the alternative pathway of the complement system when these were assessed in a fluid phase. However, C4BP was efficiently inhibiting the alternative pathway when present on the activating surface. Taken together, the disease ameliorating effect of C4BP appears to be related to inhibition of both pathways of complement. CONCLUSIONS: Although human C4BP was cleared relatively fast from the circulation and was only moderately affecting complement activity, its effect on the disease severity was substantial, suggesting that minor alterations in complement activity can have significant therapeutic value in RA.}},
  author       = {{Blom, Anna and Nandakumar, Kutty S and Holmdahl, Rikard}},
  issn         = {{1468-2060}},
  language     = {{eng}},
  pages        = {{136--142}},
  publisher    = {{BMJ Publishing Group}},
  series       = {{Annals of the Rheumatic Diseases}},
  title        = {{C4b-binding protein (C4BP) inhibits development of experimental arthritis in mice.}},
  url          = {{https://lup.lub.lu.se/search/files/5241228/1055609.pdf}},
  doi          = {{10.1136/ard.2007.085753}},
  volume       = {{68}},
  year         = {{2009}},
}