Rheumatoid arthritis (RA) is a chronic, typically progressive, autoimmune disease that primarily affects the joints although it can damage other tissues, including heart, lung, and eyes. There is currently no cure for RA and the goal of treatment is reduce joint pain and inflammation, maximise function, and minimise joint destruction and deformity. Newer biological treatments targeting components of the immune system in combination with disease-modifying antirheumatic drugs (DMARDs) are effective in preventing joint damage in some patients, but not all sufferers respond to these treatments and some may relapse despite treatment. The cause of RA remains unknown but both genetic and environmental factors are suspected to play a role.

Researchers at Imperial College have now identified a new immune trigger that may contribute to the pathology of RA. Tenascin-C is an extracellular matrix glycoprotein specifically expressed at areas of inflammation and tissue damage in inflamed rheumatoid joints. The team found that injection of tenascin-C into the joint cavity in mice caused severe joint inflammation and damage and, in a separate experiment, that mice lacking tenascin-C were protected from erosive arthritis. In cultures of cells from rheumatoid arthritis patients, tenascin-C induced synthesis of pro-inflammatory cytokines via activation of Toll-like receptor 4 (TLR4). TLR4 is one of a family of receptors that play a key role in pathogen recognition and activation of innate immunity. Stimulation of TLR4 is known to activate macrophages leading to release of TNF-α, one of the targets of existing biological agents used to treat RA patients. Previous studies had shown that mice lacking TLR4 do not show chronic joint inflammation, and blocking the interaction between tenascin-C and TLR4 may provide a new way to combat RA.

The study is published in the journal Nature Medicine.

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Rheumatoid Arthritis (RA) is a painful, chronic, progressive and disabling auto-immune disease. Newly released data has shown that a novel biologic, Actemra^™ (tocilizumab),  is superior to current standard of care in RA patients. Actemra^™ is a humanised monoclonal antibody to the interleukin-6 receptor that blocks the activity of interleukin-6, a protein that plays a major role in the RA inflammatory process. Actemra^™ is awaiting approval in the United States and Europe.  In Japan, Actemra^™ was approved for the treatment of RA in April 2008.

Other biologics are already used to treat RA and act at different points in the inflammatory process.

Orencia® (abatacept) works by reducing the activation of T-cells, which reduces the activation of other cells in the RA inflammatory process. Humera®(adalimumab), Enbrel®( etanercept) and Remicade® (infliximab) block the action of TNF-alpha, an inflammatory cytokine that leads to tissue damage. Mabthera® (rituximab) targets B cells, one of the key players in the pathogenesis of RA. Kineret® (anakinra) blocks the actions of the cytokine, IL-1.

The biologic medicines are usually prescribed together with the disease-modifying anti-rheumatic drug, methotrexate.

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