Rheumatoid arthritis (RA) is a complex autoimmune disease and exact causes are unknown. However, there is ongoing research in many areas, including genetics, hormones, infection, new drugs, and more.
RA occurs when your immune system malfunctions and attacks the membrane linings that surround your joints, called synovium. In essence, the body thinks there is an infection in the joints. This abnormal immune response creates constant inflammation in the synovium that causes intense pain, fever, swelling, and limited range of motion.
As RA worsens, inflammation thickens the synovium and destroys cartilage within the joint. The tendons and ligaments around the joints stretch, weaken, and eventually become deformed. However, proper treatment can help to slow the progression of RA.
Medical scientists don't know exactly what starts the inflammation process in RA or what determines the severity of the condition. However, it may be triggered by a combination of factors, including:
- abnormal autoimmune response
- genetic susceptibility
- environmental or biological triggers, such as viral and bacterial infections
Researchers think genetic factors play a role in RA—either by increasing the risks of getting RA, or by worsening the progress of the disease.
According to the Arthritis Foundation, scientists have identified a number of genetic markers associated with the immune response, inflammation, and RA. When present, these markers predict a 10-times-greater chance of developing RA (AF, 2012).
According to the University of Maryland Medical Center, the main genetic marker for RA is human leukocyte antigen (HLA). A number of HLA genetic forms (HLA-DRB1 and HLA-DR4 alleles) are referred to as the RA-shared epitope (UMMC, 2009).
Genetic factors don’t actually cause RA, but, they can predict whether a person is likely to get it and how serious the condition will become. Particular genetic markers can also tell your doctor how well you might respond to certain anti-rheumatic drugs.
The Possible Role of Infections in RA
Over the past two decades, research on animals has told doctors more about infections and RA. Although many types of bacteria and viruses have been studied, no single organism has been positively identified as the primary trigger for the immune response and damaging inflammation.
However, scientists do have some leads. The synovial fluid of people with RA has higher levels of antibodies linked to the common intestinal bacteria E. coli. According to the University of Maryland Medical Center, E. coli may trigger the immune system to prolong RA inflammation. Other potential viral and bacterial organisms that may trigger RA include Mycoplasma, parvovirus B19, retroviruses, mycobacteria, and Epstein-Barr virus (UMMC, 2009).
The possibility of a bacterial or viral infection triggering the immune system is an important topic of research, but there are no firm results yet.
Is it Hormonal?
Can hormones make you more susceptible to RA? Researchers have studied this question for about 20 years, but the results are still inconclusive.
What we do know is that RA is much more common in women than in men. In fact, 70 percent of people with RA are women, according to the Arthritis Foundation (AF, 2012).
In addition, women with RA tend to go into remission while they are pregnant and then experience a flare-up after giving birth. This has led researchers to study the reproductive hormones’ role in RA.
Here are some facts about hormones and RA, from the Centers from Disease Control and Prevention (CDC, 2011):
- oral contraceptives (OC): Studies performed in the early 1990s found a moderately reduced risk of RA in women who had used OCs. However, later studies did not confirm the finding. This may be because OCs in the 1960s had an 80 to 90 percent higher concentration of estrogen, which could explain the lack of association to RA in later studies.
- hormone replacement therapy (HRT): There is conflicting evidence of an association between HRT and RA.
- live birth history: Most studies have found that women who have never had a live birth have a slight to moderately higher risk of RA.
- breastfeeding: Recent population-based studies have found that RA is less common in women who breastfeed.
- menstrual history: At least two studies have observed that women with irregular periods or early menopause have a higher risk of RA.
According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases, RA research is being done in many areas today, including (NIAMS, 2009):
- immune systems
- genetic factors
- families with RA
- new drugs or drug combinations
- RA and disability
- preventing related health problems
- quality of life for people with RA
There are also published and ongoing studies about smoking and obesity as risk factors for RA.