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Joints, Muscles and Bones Rheumatoid Arthritis What causes RA?
What causes RA?
About RA

What causes RA?

Rheumatoid arthritis (RA) can affect people in different ways, and the way it develops can vary from person to person – even if they have the same diagnosis. This is why RA is often called a "heterogeneous" disease, meaning it doesn't look the same in everyone.

Autoantibodies, antibodies that the body mistakenly produces to target its own tissues, are generally an important characteristic of RA. However, they are not present in all individuals. This leaves two types of RA:1

Two text boxes side by side. Left: “Seropositive RA. RA in which autoantibodies are present in the blood. Right: Seronegative RA. RA in which autoantibodies are not present in the blood. Each with a graphic of a test tube.

Factors involved in causing RA 

RA is a complex disease and involves environmental factors that trigger disease in genetically susceptible individuals.1 Common factors include:2

“Three text boxes describing common causative factors. Left box: “Genetic factors (icon of DNA). You may carry genes that make you more likely to develop RA, even if no family members have a related immune condition.” Centre box: “Environmental factors. (icon of person smoking). Smoking increases RA risk. Being overweight may increase risk and is associated with worsening symptoms.” Right box: “Hormonal factors (icon of hormone) RA affects more women than men. RA often comes on during childbirth or onset of meopause.”

The final ‘trigger’ that causes RA onset is not yet well understood.2 If you think you are aware of the trigger or root cause of your RA, it is important to recognise that it is an unpredictable disease.

How does inflammation work in RA?

Inflammation is a natural part of the body’s immune response, designed to deal with pathogens and other harmful stimuli. However, in an autoimmune condition like RA, this response is against healthy tissue. 

RA involves inflammation of synovial tissue3, a connective tissue that lines joints and surrounding tissues.4 Proteins known as ‘cytokines’ are involved in inflammation. In RA, these proteins act as signals that trigger changes in the synovial tissue. Tumour necrosis factor alpha (TNF-α) is considered the main cytokine involved in RA.3

“The process of inflammation. Step 1. Immune cells produce cytokines, including TNF-alpha. Step 2. Cells in the synovial tissue break down important protein structures. Step 3. Cartilage and bone are progressively destroyed, and joints erode.”

This process can lead to chronic disability.3

References

  1. Smolen JS, et al. Rheumatoid arthritis. Nat Rev Dis Primers. 2018;4, 18001.
  2. Jang D-i, et al. The Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and Current TNF-α Inhibitors in Therapeutics. Int. J. Mol. Sci. 2021;22, 2719.
  3. National Rheumatoid Arthritis Society. Possible causes and risk factors. Available at: https://nras.org.uk/resource/possible-causes-and-risk-factors/. Last accessed April 2025.
  4. NIH. National Cancer Institute Dictionary of Cancer Terms. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/synovial-membrane. Last accessed April 2025.