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

Ospelt, C. et al. (2004) Toll-like receptors in rheumatoid arthritis joint destruction mediated by two distinct pathways. In: Sixth International Symposium on Advances in Targeted Therapies, Venice, Italy, 28 Apr - 2 May 2004, ii90-ii91. (doi:10.1136/ard.2004.028324)

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Abstract

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 even in the absence of cytokine producing macrophages and T and B cells.1 By analysing cytokines, matrix degrading enzymes, and signalling molecules in the SCID mouse model, we explored the factors leading to synovial activation.

Item Type:Conference Proceedings
Additional Information:Special Issue: Annals of the Rheumatic Diseases, 63 Sup. 2: ii90-ii91
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kurowska-Stolarska, Dr Mariola
Authors: Ospelt, C., Kyburz, D., Pierer, M., Seibl, R., Kurowska, M., Distler, O., Neidhart, M., Muller-Ladner, U., Pap, T., Gay, R. E., and Gay, S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Annals of the Rheumatic Diseases
Publisher:B M J Group
ISSN:0003-4967
ISSN (Online):1468-2060

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