rheumatoid arthritis

What is rheumatoid arthritis?

Rheumatoid arthritis (RA) is a progressive degenerative disease in which the connective tissue that exists throughout the body becomes inflamed. RA is an autoimmune disease in which the immune system no longer recognises cells comprising the connective tissue of the joint capsule, resulting in the launch of a rapid immune response against the affected cells. The presence of autoantibodies in the blood supports the classification of RA as an autoimmune disorder. RA can affect the joints and greatly limit mobility, and also negatively affects on the skin, blood vessels, heart and lungs. RA can lead to irreparable and permanent damage to the affected of connective tissue, due to the development of pannus scar tissue. RA is usually a disease of old age, and women are three times more likely to develop RA than men. Although swift and aggressive treatment of RA can lead to favourable outcomes for the patient, the treatment and side effects can often result in the development of extremely debilitating disorders.

Rheumatoid arthritis pathology

The degradative nature of RA begins in the synovial membrane, a sheet surrounding the synovial joint, no more than one to two cell layers thick normally. These cells comprising the synovial membrane are called synoviocytes. During the course of RA, the breakdown of the joints is mediated by cell-to-cell contacts between T-lymphocytes and monocytes, which penetrate and make contact with the synovial membrane[5]. The delicate synovial tissue de-differentiates and forms scar tissue known as a pannus, which may lead to the break down of the surrounding bone and joint tissue[6].

This degradation of the synovial membrane is also associated with an increase in the binding of CD4+ lymphocytes to endothelial cells[7]. This abnormal increase in the number of cells comprising the synovial joint creates a pathological bulkiness in the joint membrane which further compounds the problem, and subsequently causes further inflammation. This inflammation leads to the breakdown of cartilage matrix, bone and the synovial membrane and recruiting leukocytes to the affected area. This recruitment of leukocytes encourages peptide hydrolyses through activation of metal activated enzymes[8]. Cytokines, primarily tumour-necrosis factor (TNF) and interleukin (IL -1), are subsequently released from the fibroblast cells of the arthritic joint, encouraging further fibroblast proliferation, and consequently, an increased deposition of connective tissue[9].

The resultant swelling of the joints and decreased mobility is the consequence of the cytokines, TNF and IL-1 having affects on the joint, through the recruitment of increased fibroblast activity, and the attraction of lymphocytes and monocytes. However, it is this very involvement of cytokines that makes it possible to treat RA with immunotherapy, since the goal in therapy is to restore the natural levels of cytokines.



5) Gough AK, Lilley J, Eyre S, Holder RL, Emery P. Generalised Bone Loss in Patients With Early Rheumatoid Arthritis, Lancet 1994, 344: 23-7.
6) Ritchlin CT, Winchester RJ. Potential Mechanisms for Coordinate Gene Activation in the Rheumatoid Synoviocyte: Implications and Hypotheses. Spriner Seminars in Immunopathology 1989, 11: 219-34.
7) Ziff M. Role of Endothelium in Chronic Inflammatory Synovitis. Journal of Experimental Medicine 1994, 173; 183-8.
8) Ritchlin C. Fibroblast Biology. Effector Signals Released by the Synovial Fibroblast in Arthritis. Arthritis Research 2000, 2: 356-360.
9) Bucala R, Ritchlin C, Winchester R, Cerami A. Constitutive Production of Inflammatory and Mitogenic Cytokines by Rheumatoid Synovial fibroblasts. Journal of Experimental Medicine. 1991, 173: 569-574.