Thrombocytosis, elevated erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) usually correlate with the rheumatoid disease activity rather than disease severity. These laboratory tests are thus of some value in monitoring the course of the illness.

ETIOLOGY AND PATHOGENESIS

Although the etiology of rheumatoid arthritis is not yet understood, the following four factors—genetic background, abnormal immunity, environmental, and sex hormones—may play a role in concert with one another. Many causative factors have been proposed, including infectious microorganisms such as bacteria, mycobacteria, Mycoplasma, and their components and Epstein-Barr virus, parvovirus, and other viruses. Tobacco smoking has been shown to increase the citrullination of proteins and is associated with an increased risk of developing rheumatoid arthritis.

It is widely believed that rheumatoid arthritis develops in a person with a genetic predisposition following exposure to an unknown infectious agent (possibly viral). It is also possible that the illness results from an inappropriate immune response to a ubiquitous pathogenic agent. In the absence of an established cause, physicians can only evaluate each clinical and laboratory abnormality in relation to the disease and speculate on its etiologic significance.

Results of numerous studies have clarified the major role of immunologic reactions in the pathogenesis and perpetuation of rheumatoid inflammation.

Synovial T Lymphocytes. In the synovium of chronic rheumatoid arthritis, T lymphocytes constitute about 50% of the synovial cells and are mostly CD4⁺ T lymphocytes with an activated surface phenotype, and high expression of HLA-DR antigens and CD27. CD4⁺CD27⁺ T lymphocytes provide B-lymphocyte help, resulting in antibody production in the synovium.

Synovial B Lymphocytes. Many rheumatoid synovial tissues exhibit a diffuse infiltration with mononuclear cells. There are discrete lymphoid follicles populated by B lymphocytes in the sublining region. B lymphocytes and plasma cells constitute only about 5% of the rheumatoid synovium; however, their hyperactivity is viewed as a key player in the initiation and perpetuation of the early rheumatoid arthritis. As a result, rheumatoid factor and anti-CCP antibodies are detected in the synovial fluid and serum.