View on rheumatoid arthritis in XXI century

Failure of immunologic self-tolerance leads to the development of rheumatoid arthritis. Althougt the exact pathogenesis of rheumatoid arthritis is not understood yet, it has been thought that inappropriate activation of the immune system plays a central part. The cascade of events is complex, involving multiple cells of the immune system and cytokines wich promote the activation of fibroblasts, chondrocytes and osteokclasts, and the production of matrix metalloproteinases and other molecules involved in the tissue destruction. Because T cells play a central role in pathogenesis rheumatoid arthritis therapies are based through their inactivation or by changing their function. Now the most effectivness therapies are these using TNF-α blokers in combination with methotrexate, but they have limitations and therefore the search for futher targets is warranted as against IL-6 and other cytokines and molecules expressed on B-cells and T-cells. One way of blocking the stimulation T-cells is blocking the co-stimulation molecules CD28. CD28 blockers are monoclonal antibodies to CD80 and CD86 or CTLA-4 constructs.