The cause of rheumatoid arthritis (RA) is not known. Researchers suspect that a combination of genetic susceptibility and other factors — viral or bacterial infection, hormones, or environmental factors — is responsible for RA. However, no one really knows what makes the immune system turn against body.
There are several genes associated with RA, all of which have to do with immune response and inflammation. People with one genetic marker — the HLA shared epitope — are five times more likely than others to develop rheumatoid arthritis. Other genes related to RA are called STAT4, TRAF1/C5, PTPN22, and OLIG3/TNFAIP3. However, not everyone with these genes develops RA and not everyone with RA has one of these genes, which means that some other cause combines with genetics to trigger the condition.
Rheumatoid arthritis is much more common in women than in men, and women with RA tend to go into remission while they are pregnant and then experience a flare-up after giving birth. Breastfeeding is also associated with worsening of RA symptoms. This is strong evidence that female hormones have something to do with RA, but the relationship is not yet understood.
In animal studies performed over the last couple of decades, the introduction of common bacteria (such as bacteria found in the stomachs of most people) caused arthritis symptoms. The possibility of bacterial or viral infection triggering the immune system is an important topic of research in many autoimmune diseases including RA, but there are no firm results yet.