Rheumatoid arthritis is one of the most common forms of arthritis, affecting 1.3 million adults in the United States. It’s an autoimmune disease, meaning the immune system mistakenly attacks healthy cells in the body instead of protecting them. A healthy immune system protects against germs and sends fighter cells to attack them. But with autoimmune diseases, the immune system treats normal cells like foreign cells and releases autoantibodies that attack healthy cells. Autoantibodies are antibodies that mistakenly target a person’s own tissue or organs. Experts are unsure about what causes autoimmune diseases, but one theory is that microorganisms like bacteria and viruses trigger changes that confuse the immune system.
When you have RA, the immune system sends antibodies to the lining of your joints. The antibodies then attack the tissue surrounding the joints. This causes soreness and inflammation in the layer of cells, called the synovium, that covers your joints. The synovium releases chemicals that can damage bones, cartilage, ligaments, and tendons. If left untreated, these chemicals can cause the joint to lose its shape and alignment. Over time, these chemicals can destroy the joint completely.
RA is 2.5 times more common in women than men. While it can develop at any age, it most commonly occurs in people between the ages of 20 and 50. Late-onset RA or elderly-onset RA occurs when it develops in people between the ages of 60 and 65.
Symptoms of rheumatoid arthritis include:
- Joint stiffness that is often worse in the morning or after periods of inactivity
- Joint pain or tenderness
- Swelling
- Fatigue
- Loss of joint function and mobility
While the exact causes of rheumatoid arthritis are unknown, researchers believe a combination of genetic and environmental factors can trigger rheumatoid arthritis.
Genetics
RA isn’t an inherited disease, but it is possible to carry genes that put you at an increased risk for developing the condition. These are known as susceptibility genes. You may have susceptibility genes even if no one in your family has RA. Studies have found that relatives of patients with RA have an increased risk of developing the disease. You may also have genetic markers for RA that haven’t been activated. These can be triggered by something else, like smoking, and increase your risk of developing the condition.
One study found that first-degree relatives of patients with RA are three times more likely to develop RA when compared to first-degree relatives of people from the general population. First-degree relatives are blood relatives with whom you share about 50% of your genes and include parents, siblings, and children.
Studies of twins have provided further evidence that genes contribute to RA risk. In Identical twins, both were more likely to have RA compared to fraternal (non-identical) twins. Identical twins share 100% of the same genes, while fraternal twins share 50% of the same genes. About 15% of identical twins will develop RA, compared to 4% of non-identical twins. Using data from twin studies, researchers estimate that genetics account for 53% to 68% of RA risk.
Researchers found over 100 genetic changes that commonly occur in patients with rheumatoid arthritis. Research is being done to understand what these genes do, how they interact with each other, and what environmental factors cause RA. Some of these genes are involved in other autoimmune diseases like multiple sclerosis. These shared genes may be why some people develop more than one autoimmune disorder.
HLA-DRB1
The HLA-DRB1 gene belongs to a family of genes known as the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body’s own proteins from those made by foreign invaders. HLA-DRB1 provides instructions for making a protein that plays a key role in the immune system.
HLA-DRB1 is the strongest known genetic risk factor for the development of RA and several variations of this gene are associated with an increased risk of developing the condition. How HLA-DRB1 increases the risk of RA is unclear, however researchers believe it’s related to changes in peptide binding that cause an unusual immune response. The protein HLA-DRB1 produces attaches to a protein produced by the HLA-DRA gene to form a complex that triggers the body’s immune response.
There are a few variations of HLA-DRB1 that may decrease the risk of developing RA. However, it is unclear why those variations are protective.
HLA-DR4
HLA-DR4 is a genetic marker that is a genetic anomaly. Its function is to distinguish the body’s own cells from foreign invaders. If HLA-DR4 is found in white blood cells, there is a risk of developing RA. In rheumatoid arthritis patients of European ancestry, as many as 60% to 70% carry the HLA-DR4 gene. In the general population, 30% of RA patients have this gene.
PTPN22
Protein tyrosine phosphatase 22 (PTPN22) is involved in signaling that helps control the activity of immune system cells called T cells. These cells identify foreign substances and help protect the body against infection. This gene contributes to the development and progression of RA.
STAT4
The STAT4 gene provides instructions for a protein that attaches to specific regions of the DNA to control the activity of certain genes. When the STAT4 protein is turned on, it increases the activity of genes that help T cells mature into specialized T cells. These specialized cells produce specific immune system proteins called cytokines and stimulate other immune cells to fight off foreign invaders. A set of DNA variations in STAT4 are associated with an increased risk of RA.
Environmental Factors
There are many things in the environment that can affect our health. There are several environmental factors that have a relationship with rheumatoid arthritis. Studies have found that environmental exposures such as smoking and alcohol intake can change RA risk.
Smoking
While the link between smoking and rheumatoid arthritis isn’t well understood, researchers think it triggers faulty immune system functioning in people who are genetically predisposed to RA. A 2010 study found that the risk of developing RA is about 1.3 times greater for smokers than for non-smokers.
Smoking reduces immune system function and can put people with RA at a greater risk of developing other autoimmune diseases. Nicotine, the addictive substance in tobacco products, suppresses the immune system. It increases inflammation and decreases the antibody-forming cell response of certain white blood cells.
Smoking can also increase oxidative stress in the body. Oxidative stress is an imbalance between antioxidants and free radicals in the body. Free radicals are unstable molecules that can damage the cells in your body. Internal sources of free radicals are activated by cigarette smoke. This damage can increase the risk of diseases like rheumatoid arthritis.
People who smoke also have an increased risk of more severe RA and may be less likely to experience remission. Smoking also reduces the effectiveness of certain drugs used to treat RA. Smoking may prevent people with RA from engaging in activities that can relieve symptoms, such as exercise.
People with RA who smoke may be making their condition worse. Quitting smoking is not only beneficial for RA but can help improve overall health.
Alcohol Use
Alcohol intake is also linked to rheumatoid arthritis, though the research is mixed depending on how much and how often someone drinks. Some research has found that alcohol use may reduce RA symptoms. A 2015 review concludes that moderate drinking can reduce certain inflammation markers like c-reactive protein and interleukin-6. Another study looked at the effects of drinking alcohol in 873 people with RA. The study showed that moderate alcohol consumption is associated with reduced disease severity.
While moderate amounts of alcohol may suppress inflammation and reduce RA symptoms, heavy or binge drinking can negatively impact your health. Drinking too much alcohol can cause damage to the gut and liver, leading to widespread inflammation. It can also lead to misuse and alcohol dependency.
The Center for Disease Control (CDC) states that no one should start drinking for any potential health benefits. It’s also important to know that alcohol doesn’t react well to many RA medications. Drinking alcohol while taking an NSAID can increase your risk of stomach bleeding and liver damage. If you’re taking methotrexate to help control your RA, rheumatologists recommend limiting alcohol consumption to no more than two glasses per month.
If you are going to drink alcohol, make sure to speak with your doctor about the right amount of alcohol for you. A small amount is generally safe for most people with R, but it may also increase your risk of certain health conditions.
Hormonal Factors
Rheumatoid arthritis is more common in women than men, suggesting hormones are a factor in the development of RA. Several studies have shown an association between pregnancy and breastfeeding and RA risk.
Women who have never given birth may have a higher risk of developing RA than women who have given birth. However, the protective effect of pregnancy appears to decrease over the years. While the reason that childbirth is a protective factor is unclear, one theory is that fetal cells transmitted to the mother during pregnancy lower RA risk. Fetal cells are genetically different from the mother’s cells because they contain half of the father’s genes. If the cells carry genes that are associated with a lower risk of RA, they could be passed on to the mother and lower her risk of developing the disease.
Another theory suggests that hormonal changes that occur during pregnancy play a role in the development of RA. Hormones like cortisol, estrogen, and progesterone increase during pregnancy. Cortisol is a stress hormone that regulates the immune response. Estrogen is a group of hormones that regulates the menstrual cycle and helps with bone and heart health. Progesterone is a steroid hormone that plays a role in the menstrual cycle and early pregnancy.
A 2010 study found that women who had given birth to at least one child were 39% less likely to have RA than women who had never been pregnant. The number of pregnancies and children did not appear to influence the risk of RA. The study accounted for factors like age and oral contraceptive use. Oral contraceptives use has been linked to a lower risk of developing RA.
The study also found that women who had given birth within the past five years were 71% less likely to have RA compared to non-childbearing women. However, women who had last given birth more than 15 years ago only had a 24% lower risk. Fetal cells can remain for decades, but as they age, their protection begins to wear off.
Studies have shown that breastfeeding for one to two years decreased a woman’s RA risk by 20% compared to women who never breastfed. Breastfeeding for at least two years decreased the risk by 50%. This is the total amount of time spent breastfeeding all children, not just one. Breastfeeding for less than one year did not decrease RA risk.
Diet
While diet alone can’t cause rheumatoid arthritis, it can be a contributing factor. RA develops when an autoimmune response is triggered by certain factors in a person who is genetically predisposed to the condition. Food can serve as that inflammatory trigger.
Diets high in saturated fats, sodium, and sugar are all associated with an increased risk of RA and worsening symptoms. This is because these foods are linked to increased levels of inflammation. Eating too many of these kinds of food can also lead to other chronic conditions like obesity, diabetes, and heart disease. Following a low-fat, anti-inflammatory diet can help reduce the risk of developing RA and other chronic conditions. It may also help reduce RA symptoms.
Get the Support You Need
No matter the cause, living with rheumatoid arthritis can be difficult. You may experience symptoms at inconvenient times and may make it difficult to do the things you used to.
If you are living with rheumatoid arthritis, know that you’re not alone. At PatientsLikeMe, there are over 300,000 patients just like you who are also living with RA. Join them today and share your experience with the condition.
