Causes:

The exact causes of rheumatoid arthritis are unknown. Rheumatoid arthritis is most likely triggered by a combination of factors, including an abnormal autoimmune response, genetic susceptibility, and some environmental or biologic trigger, such as a viral infection or hormonal changes.

The Immune Response and Inflammatory Process

The Normal Immune System Response. The inflammatory process is a byproduct of the activity of the body's immune system, which fights infection and heals wounds and injuries:

• When an injury or an infection occurs, white blood cells are mobilized to rid the body of any foreign proteins, such as a virus.
• The masses of blood cells that gather at the injured or infected site produce factors to repair wounds, clot the blood, and fight any infections.
• In the process the surrounding area becomes inflamed and some healthy tissue is injured. The immune system is then called upon to repair wounds by clotting off any bleeding blood vessel and initiating fiber-like patches to the tissue.
• Under normal conditions, the immune system has other special factors that control and limit this inflammatory process.

The Infection Fighters. Two important components of the immune system that play a role in the inflammation associated with rheumatoid arthritis are B cells and T cells, both of which belong to a family of immune cells called lymphocytes.

If the T cell recognizes an antigen as "non-self," it will produce chemicals (cytokines) that cause B cells to multiply and release many immune proteins (antibodies). These antibodies circulate widely in the bloodstream, recognizing the foreign particles and triggering inflammation in order to rid the body of the invasion.

For reasons that are still not completely understood, both the T cells and the B cells become overactive in patients with RA.

An antigen is a substance that can provoke an immune response. Typically antigens are substances not usually found in the body.

Genetic Factors

Genetic factors may play some role in RA either in terms of increasing susceptibility to developing the condition or by worsening the disease process but are clearly not the only important factors. The main genetic marker identified with rheumatoid arthritis is HLA (human leukocyte antigen).

A number of HLA genetic forms called HLA-DRB1 and HLA-DR4 alleles are referred to as the RA-shared epitope because of their association with rheumatoid arthritis. These genetic factors do not cause RA, but they may make the disease more severe once it has developed. Genetic variations in the HLA region may also predict drug treatment response to etanercept and the disease-modifying anti-rheumatic drug methotrexate.

Environmental Triggers

Infections. Although many bacteria and viruses have been studied, no single organism has been proven to be the primary trigger for the autoimmune response and subsequent damaging inflammation. Higher than average levels of antibodies that react with the common intestinal bacteria E. coli have appeared in the synovial fluid of people with RA. Some researchers think they may stimulate the immune system to prolong RA once the disease has been triggered by some other initial infection. Other potential triggers include Mycoplasma, parvovirus B19, retroviruses, mycobacteria, and Epstein-Barr virus.