Causes of Rheumatoid Arthritis

The exact cause of RA is not known, although there are factors that can contribute to the development and severity of this inflammatory arthritic disease.

The exact cause of rheumatoid arthritis (RA) is not yet known, although scientists have identified factors that contribute to the disease. They believe a combination of factors is involved in triggering the onset RA. Some of these factors include the following:

  • Immune system dysfunction
  • Rheumatoid factor
  • Age
  • Gender
  • Heredity
  • Bacterial and/or viral infection
  • Environment
  • Smoking
  • Obesity

photo album of old pictures of family membersHeredity may play a role in development of rheumatoid arthritis in some people. Photo Source:

Immune System Dysfunction

The immune system is normally the body’s defense against antigens (ie, foreign invaders), which include different types of bacteria, viruses, and toxins.  When confronted, the immune system triggers an inflammatory response to antigens. The inflammatory response is one way the body fights to rid itself of—for example— invading bacteria.  However, in rheumatoid arthritis the immune system may recognize normal cells and tissues as the invaders and launches an attack on those healthy cells and tissues causing autoimmune disease.

  • T cells and B cells are two types of white blood cells involved in rheumatoid arthritis. The T cells release cytokines (chemicals that play a role in the inflammatory response) and cause the B cells to release antibodies (immune proteins), which causes inflammation.

Rheumatoid Factor

The rheumatoid factor (RF) is a normal component in blood. About 80% of patients with RA have higher blood levels of rheumatoid factor (RF); a group of antibodies that accumulate in the synovium (joint lining); those patients are seropositive. Seropositive means the patient’s blood (sero or serum) is positive for the rheumatoid factor. However, not everyone with RA is seropositive, and people who don’t have rheumatoid arthritis can also be seropositive.


Rheumatoid arthritis can develop at any stage of life, but onset is usually between 30 and 60 years of age in women; men tend to develop RA later in life.


Women are more likely to develop RA than men, but researchers aren’t sure why. Hormones, or perhaps changes or deficiencies in certain hormones, may be involved. Sometimes, the symptoms of improve during pregnancy. Research suggests that hormones present during pregnancy may alter the effects of RA; specifically, molecules in the immune system, interleukin 12 (IL-12) and tumor necrosis factor-alpha (TNFα) are affected by hormonal changes.

Breastfeeding and contraceptive use may affect the immune system as well, causing RA to flare up.


According to researchers, rheumatoid arthritis isn’t hereditary, but certain genetic markers—human leukocyte antigens, or HLAS (leukocytes are white blood cells)—are believed to play a role. People with those markers have 5 times the risk for developing RA than individuals without them; they also may have a more severe course of the disease. One such marker, HLA-DR4, is present in the majority of patients. Other genes increase the risk of RA as well.

As with the rheumatoid factor, the presence of genetic markers does not mean you have or will develop RA. Many people with RA don’t have genetic markers. Scientists say more than one gene is involved, and that genetic makeup is only one ingredient in the mix.

Bacterial or Viral Infection

Some researchers believe that certain infections can trigger the onset of RA. If other factors are present–such as the HLA-DR4 gene—a person could develop RA. In other words, an infection could “turn on” the marker’s effect on the immune system.

Scientists have studied many bacteria and viruses, but so far, they haven’t identified any of those as a cause or trigger of RA. Some RA patients have high levels of antibodies against E coli (which normally lives in the digestive tract) in their synovial fluid. Other organisms that have a possible connection with RA include Epstein-Barr virus, Mycoplasma species, and others.

Environmental Factors

It is believed that something needs to happen to trigger the development of RA in susceptible individuals. Researchers have suggested several factors, but none has been identified to date.


Heavy smoking over years is a considerable risk factor. A study performed in Sweden found that smoking could be responsible for up to 20% of cases of RA, and even more in people who carried a certain protein in their blood. In heavy smokers, the risk remains high even 20 years after they quit.


According to a study conducted at the Mayo Clinic, persons with obesity are 25% more likely to develop rheumatoid arthritis than people of normal weight.

In Summary…

As mentioned earlier, no single factor causes rheumatoid arthrits; rather, a combination of factors is responsible for causing the cascade that triggers joint inflammation. RA seems to be the result of a chain reaction.

Updated on: 07/25/19
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