Metastasis-inducing S100A4 protein is associated with the disease activity of rheumatoid arthritis
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19828600
DOI
10.1093/rheumatology/kep316
PII: kep316
Knihovny.cz E-resources
- MeSH
- Adalimumab MeSH
- Antirheumatic Agents therapeutic use MeSH
- Biomarkers blood MeSH
- Adult MeSH
- Antibodies, Monoclonal, Humanized MeSH
- Cells, Cultured MeSH
- Middle Aged MeSH
- Humans MeSH
- RNA, Messenger genetics MeSH
- Monocytes drug effects immunology MeSH
- Antibodies, Monoclonal therapeutic use MeSH
- Reverse Transcriptase Polymerase Chain Reaction methods MeSH
- S100 Proteins blood pharmacology MeSH
- Arthritis, Rheumatoid blood drug therapy MeSH
- S100 Calcium-Binding Protein A4 MeSH
- Severity of Illness Index MeSH
- Tumor Necrosis Factor-alpha antagonists & inhibitors biosynthesis genetics MeSH
- Up-Regulation drug effects immunology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Adalimumab MeSH
- Antirheumatic Agents MeSH
- Biomarkers MeSH
- Antibodies, Monoclonal, Humanized MeSH
- RNA, Messenger MeSH
- Antibodies, Monoclonal MeSH
- S100 Proteins MeSH
- S100 Calcium-Binding Protein A4 MeSH
- S100A4 protein, human MeSH Browser
- Tumor Necrosis Factor-alpha MeSH
OBJECTIVES: To evaluate the association between metastasis-inducing protein S100A4 and disease activity in patients with RA, and to demonstrate the effect of TNF-alpha blocking therapy on plasma levels of S100A4 in these patients. METHODS: Plasma levels of the S100A4 protein were analysed in 40 anti-TNF-alpha naive patients with active RA. Of the 40 patients, 25 were treated with adalimumab and monitored over time. The conformational form of S100A4 was analysed using size-exclusion gel chromatography. TNF-alpha mRNA expression and protein synthesis were analysed by RT-PCR and ELISA, respectively. RESULTS: Baseline levels of S100A4 were significantly correlated with disease activity in RA patients (r = 0.41; P < 0.01). After 12 weeks of treatment with adalimumab, there was an obvious shift in the conformations of S100A4 from the multimeric to the dimeric forms, whereas the total levels of the S100A4 protein remained unchanged. This suggests that the bioactive (multimer) S100A4 may decline in response to successful treatment with adalimumab. In addition, we showed significant up-regulation of TNF-alpha mRNA (P < 0.01), and protein release to the cell culture medium of monocytes stimulated with the S100A4 multimer compared with those treated with the dimer and to the unstimulated monocytes (P < 0.001). CONCLUSIONS: This is the first study to show that the levels of the S100A4 protein are correlated with RA disease activity. Furthermore, only the bioactive form, but not the total amount of S100A4, decreases after successful TNF-alpha blocking therapy in patients with RA. These data support an important role for the S100A4 multimer in the pathogenesis of RA.
References provided by Crossref.org
S100A4 is elevated in axial spondyloarthritis: a potential link to disease severity
