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Decreased levels of soluble receptor for advanced glycation end products in patients with rheumatoid arthritis indicating deficient inflammatory control

Pullerits, R; Bokarewa, M; Dahlberg, Leif LU and Tarkowski, A (2005) In Arthritis Research and Therapy 7(4). p.817-824
Abstract
The receptor for advanced glycation end products ( RAGE) is a member of the immunoglobulin superfamily being expressed as a cell surface molecule and binding a variety of ligands. One of these ligands is high-mobility group box chromosomal protein 1, a potent proinflammatory cytokine, expression of which is increased in synovial tissue and in synovial fluid of rheumatoid arthritis (RA) patients. The interaction of high-mobility group box chromosomal protein 1 with cell-surface RAGE leads to an inflammatory response. In contrast, the presence of soluble RAGE (sRAGE) may abrogate cellular activation since the ligand is bound prior to interaction with the surface receptor. Our aim was to analyse to what extent sRAGE is present in patients... (More)
The receptor for advanced glycation end products ( RAGE) is a member of the immunoglobulin superfamily being expressed as a cell surface molecule and binding a variety of ligands. One of these ligands is high-mobility group box chromosomal protein 1, a potent proinflammatory cytokine, expression of which is increased in synovial tissue and in synovial fluid of rheumatoid arthritis (RA) patients. The interaction of high-mobility group box chromosomal protein 1 with cell-surface RAGE leads to an inflammatory response. In contrast, the presence of soluble RAGE (sRAGE) may abrogate cellular activation since the ligand is bound prior to interaction with the surface receptor. Our aim was to analyse to what extent sRAGE is present in patients with chronic joint inflammation (RA) as compared with patients with non-inflammatory joint disease and with healthy subjects, and to assess whether there is an association between sRAGE levels and disease characteristics. Matching samples of blood and synovial fluid were collected from 62 patients with RA with acute joint effusion. Blood from 45 healthy individuals, synovial fluid samples from 33 patients with non-inflammatory joint diseases and blood from six patients with non-inflammatory joint diseases were used for comparison. sRAGE levels were analysed using an ELISA. RA patients displayed significantly decreased blood levels of sRAGE (871 +/- 66 pg/ml, P < 0.0001) as compared with healthy controls (1290 +/- 78 pg/ml) and with patients with noninflammatory joint disease (1569 +/- 168 pg/ml). Importantly, sRAGE levels in the synovial fluid of RA patients (379 +/- 36 pg/ ml) were lower than in corresponding blood samples and correlated significantly with blood sRAGE. Interestingly, a significantly higher sRAGE level was found in synovial fluid of RA patients treated with methotrexate as compared with patients without disease-modifying anti-rheumatic treatment. We conclude that a decreased level of sRAGE in patients with RA might increase the propensity towards inflammation, whereas treatment with methotrexate counteracts this feature. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Arthritis Research and Therapy
volume
7
issue
4
pages
817 - 824
publisher
BioMed Central
external identifiers
  • pmid:15987483
  • wos:000231020100019
  • scopus:21644441444
ISSN
1478-6362
DOI
10.1186/ar1749
language
English
LU publication?
yes
id
7053ea5c-913d-4989-b700-45606f22f559 (old id 229836)
date added to LUP
2007-08-10 08:51:33
date last changed
2017-09-17 04:59:49
@article{7053ea5c-913d-4989-b700-45606f22f559,
  abstract     = {The receptor for advanced glycation end products ( RAGE) is a member of the immunoglobulin superfamily being expressed as a cell surface molecule and binding a variety of ligands. One of these ligands is high-mobility group box chromosomal protein 1, a potent proinflammatory cytokine, expression of which is increased in synovial tissue and in synovial fluid of rheumatoid arthritis (RA) patients. The interaction of high-mobility group box chromosomal protein 1 with cell-surface RAGE leads to an inflammatory response. In contrast, the presence of soluble RAGE (sRAGE) may abrogate cellular activation since the ligand is bound prior to interaction with the surface receptor. Our aim was to analyse to what extent sRAGE is present in patients with chronic joint inflammation (RA) as compared with patients with non-inflammatory joint disease and with healthy subjects, and to assess whether there is an association between sRAGE levels and disease characteristics. Matching samples of blood and synovial fluid were collected from 62 patients with RA with acute joint effusion. Blood from 45 healthy individuals, synovial fluid samples from 33 patients with non-inflammatory joint diseases and blood from six patients with non-inflammatory joint diseases were used for comparison. sRAGE levels were analysed using an ELISA. RA patients displayed significantly decreased blood levels of sRAGE (871 +/- 66 pg/ml, P &lt; 0.0001) as compared with healthy controls (1290 +/- 78 pg/ml) and with patients with noninflammatory joint disease (1569 +/- 168 pg/ml). Importantly, sRAGE levels in the synovial fluid of RA patients (379 +/- 36 pg/ ml) were lower than in corresponding blood samples and correlated significantly with blood sRAGE. Interestingly, a significantly higher sRAGE level was found in synovial fluid of RA patients treated with methotrexate as compared with patients without disease-modifying anti-rheumatic treatment. We conclude that a decreased level of sRAGE in patients with RA might increase the propensity towards inflammation, whereas treatment with methotrexate counteracts this feature.},
  author       = {Pullerits, R and Bokarewa, M and Dahlberg, Leif and Tarkowski, A},
  issn         = {1478-6362},
  language     = {eng},
  number       = {4},
  pages        = {817--824},
  publisher    = {BioMed Central},
  series       = {Arthritis Research and Therapy},
  title        = {Decreased levels of soluble receptor for advanced glycation end products in patients with rheumatoid arthritis indicating deficient inflammatory control},
  url          = {http://dx.doi.org/10.1186/ar1749},
  volume       = {7},
  year         = {2005},
}