What Causes Rheumatoid Arthritis?

Patient Expert
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The cause of rheumatoid arthritis (RA) remains unknown. Much like a large jigsaw puzzle with no box, we have certain pieces of information but not the whole picture. Every year researchers chip away at the mystery, revealing more about what contributes to the development of this autoimmune disease (the pathogenesis of RA). We know that RA is triggered by a complex interaction between genetic and environmental factors and a number of these have been identified or are being investigated.


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Genetic variation

Scientists believe that RA is in large part based on heritability. That is, the amount of variation in a population (such as people with RA) that is due to different genetic factors. In fact, the risk of developing RA is estimated to be 60 percent based on heritability. This means that you may be more likely to develop RA if someone in your family already has the condition. The risk is highest in first-degree relatives (children and siblings), but still estimated to be less than 20 percent or lower.


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Genes, not jeans, part one

When variations occur in genes involved in immune system function, the risk of RA may increase. The human leukocyte antigen (HLA) genes produce proteins that enable your immune system to tell the difference between your body’s own proteins and foreign ones. This helps you fight infection. When variations occur, it affects the ability to differentiate between these. The HLA genes contribute approximately 11-37 percent of the risk and the HLA-DRB1 gene is particularly involved.


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Genes, not jeans, part two

Although HLA genes are particularly involved in increasing the risk of RA, other genes have also been identified as playing a role. These include PTPN22 (T-cell activation), TRAF1 (tumor necrosis factor signaling) and STAT4 (T-cell activation). The genetic picture of RA is complex, but doesn’t appear to cause the condition, instead increasing the risk. Environmental factors then trigger the immune response that leads to RA in some people who are genetically predisposed to develop RA.


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Hormones

Hormones are one of the known factors in RA, although we don’t know exactly what role they play. Three times as many women as men have RA and the condition often develops during childbearing years. Moreover, the majority of pregnant women with RA go into remission until approximately six weeks after childbirth. Anecdotal evidence also seems to suggest that RA symptoms flare during premenstrual syndrome PMS.


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Smoking

Many studies have shown that smoking — as well as exposure to second-hand smoke — is one of the most important environmental factors in the pathogenesis of RA, playing a role in both the risk of developing the condition, as well as its severity. The exact mechanism is unknown, but it is suspected that smoking interferes with immune function. Studies have also found that smoking may interfere with the functioning of certain RA medications, particularly anti-TNF drugs, further indicating the link.


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Answers in the microbiome

The microbiome is the name for the microbes that live in your intestinal tract. There are two to three pounds worth, containing as many as 1,000 species. That might sound gross, but there is evidence that they play an important role in your health. Several families of microbes have been shown to be more dominant in both animals and humans with RA. It is theorized that the reason some people with RA respond to diet is that these different types of food change the microbiome.


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How dental health is involved

Another suspect in the development of RA is your dental health, specifically periodontal disease. One study showed that the bacteria A. actinomycetemcomitans was present in the majority of people with RA. The theory is that the bacteria responsible for chronic, inflammation may be part of the process that triggers the development of RA. As well, people who already have RA are often more likely to experience periodontal disease.


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Early development and environment

A number of factors in our early development and environment may also play a role in adult-onset RA. Some of these include high birth weight, not sharing a room in childhood (and therefore being exposed to less infection), as well as the connection between RA and allergies. Factors associated with less incidence of RA include breastfeeding, sharing a room, lower socioeconomic status, and lower birth order.


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Air pollution

Pollution contributes to a number of problems, including a higher risk of developing RA. A number of studies have shown that there is a link between RA and pollutants from traffic, wood smoke, and diesel exhaust. Although the exact role of pollution is still not identified, this link and the connection to smoking has led to theories that the first stages of inflammation and creation of RA-related autoantibodies may happen in the lungs.


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Employment

A recent Swedish study showed that RA may be related to the job you do. The findings showed that men who worked in bricklaying and jobs dealing with concrete were up to three times more likely to develop the condition than those who worked in an administrative setting. The researchers suspected the cause was exposure to harmful airborne substances. Previous studies have identified that exposure to silica in jobs that perform drilling or crushing stone increases the risk of RA.


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Insecticides and more

Dealing with insecticides both as part of agriculture and in, for instance, growing a garden, has been linked to an increased risk of developing RA and lupus. Other substances that may be involved in triggering RA include mercury, lead, solvents, alcohol use and more. Efforts are continuing to confirm and explore the role that these and many other environmental factors have in the immune response that leads to developing RA.


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Geography

Where you live is also being investigated as a factor that may increase your risk of developing RA. Research based on the Nurses’ Health Study found that women living in the Midwest and New England were up to 45 percent more likely to develop RA than women who lived in the western mountain and Pacific regions of the United States. The investigators theorized that this was linked to air pollution, which is higher in the more densely populated New England and Midwest regions.


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Trauma

Studies indicate that the onset of RA can be associated with an event causing physical trauma. This could be a car accident, broken bone, or even surgery, between six months and two years prior to the appearance of the condition. One theory of the reason behind this is that the trauma potentially changes or releases antigens from connective tissue, which then contributes to the development of inflammation.


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Are you doomed?

Reading about all the factors that are or may be part of developing RA can make you feel helpless. Are you doomed? Not at all. Keep in mind that RA is a result of an intricate interaction between genetic and environmental factors. This may put you at greater risk for RA, but we cannot yet predict who will develop RA and who will not. You may have one or more of all of these factors in your life and still not get RA. If you have questions about this topic, talk to your doctor.