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New targets IV

Toll-like receptors in rheumatoid arthritis joint destruction mediated by two distinct pathways

C Ospelt, D Kyburz, M Pierer, R Seibl, M Kurowska, O Distler, M Neidhart, U Muller-Ladner, T Pap, R E Gay, S Gay

WHO Collaborating Center for Molecular Biology and Novel Therapeutic Strategies for Rheumatic Diseases, Clinic for Rheumatology, University Hospital, Zurich, Switzerland

Correspondence to:
Correspondence to:
S Gay
WHO Collaborating Center for Molecular Biology and Novel Therapeutic Strategies for Rheumatic Diseases, Clinic for Rheumatology, University Hospital, Gloriastrasse 25, CH-8091 Zurich, Switzerland; Steffen.Gay@usz.ch

Abbreviations: RA, rheumatoid arthritis; RA-SF, RA synovial fibroblast; SCID, severe combined immunodeficiency, TLR, toll-like receptor

Keywords: toll-like receptors; joint destruction; rheumatoid arthritis; synovial fibroblast; cytokine independent pathway; cytokine dependent pathway

The first 150 words of the full text of this article appear below.

Novel therapies, in particular biological agents, have resulted in major breakthroughs in the treatment of rheumatoid arthritis (RA). However, none of the new and promising biologicals has resulted in an American College of Rheumatology (ACR) 70 above 50%, and none of them has shown sustained benefit after termination of therapy. These results are based on the fact that all these agents target the inflammatory cells in the joint, including macrophages, T and B lymphocytes, or vascular endothelium but not the activated synovial fibroblasts. RA synovial fibroblasts (RA-SFs) have to be considered key cells in joint destruction since they differ in their morphology and their biological behaviour from normal synoviocytes and, most importantly, show invasive growth into adjacent tissue.

We have shown that RA-SFs maintain their activated phenotype independently of inflammatory cells and cytokines, considering that they invade human cartilage in the severe combined immunodeficiency (SCID) mouse model . . . [Full text of this article]

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