RESEARCH - Metastasis-inducing S100A4 protein is associated with the disease activity of RA

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Rheumatology Advance Access published online on October 14, 2009

Rheumatology, doi:10.1093/rheumatology/kep316

Metastasis-inducing S100A4 protein is associated with the disease

activity of rheumatoid arthritis

Lucie Olejková1, m Grigorian2, Hana Hulejová1, Jií Vencovsk1,

Karel Pavelka1, Jörg Klingelhöfer2, Steffen Gay3, Michel Neidhart3,

Hana Brabcová4, Such4 and Ladislav enolt1

1Department of Rheumatology of the First Faculty of Medicine,

Institute of Rheumatology and Connective Tissue Research Laboratory,

University in Prague, Prague, Czech Republic, 2Institute of

Cancer Biology, Danish Cancer Society, Copenhagen, Denmark, 3Center of

Experimental Rheumatology, University Hospital Zurich and Zurich

Center of Integrative Human Physiology, Zurich, Switzerland and

4Department of Clinical Pharmacology, Teaching Hospital, Pilsen, Czech

Republic.

Abstract

Objectives. To evaluate the association between metastasis-inducing

protein S100A4 and disease activity in patients with RA, and to

demonstrate the effect of TNF- blocking therapy on plasma levels of

S100A4 in these patients.

Methods. Plasma levels of the S100A4 protein were analysed in 40

anti-TNF- 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- 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- 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- blocking therapy in patients with RA. These data

support an important role for the S100A4 multimer in the pathogenesis

of RA.

http://rheumatology.oxfordjournals.org/cgi/content/abstract/kep316v1?papetoc

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