Rheumatoid factor (RF) is a type of antibody, an immune system protein that helps the body fight foreign substances like bacteria and viruses, called antigens. Antibodies, also known as immunoglobulins, work by binding to the surface of the antigen, stimulating the immune system to attack it. Like some other antibodies, RF can also mistakenly target the body’s own cells.
Not everyone has RF in their blood; and if you do, it may have a beneficial effect. For example, your body may produce RF in response to certain bacterial toxins and viruses, such as lipopolysaccharides and Epstein-Barr virus, respectively. Commonly, however, RF attaches to the body’s own cells, sparking an immune reaction and inflammation of the synovium, the layer of soft tissue on the inner surfaces of your joints.
High concentrations of RF in the joints leads to the autoimmune disease rheumatoid arthritis (RA). An autoimmune disease is one in which the body attacks its own tissues. Rheumatoid factors are also associated with a wide range of other autoimmune and non-autoimmune diseases.
The body produces five different types of antibodies, which differ by their location and function:
IgA is found in various secretions, including saliva, tears, mucus, breast milk, and intestinal fluid, and it protects against ingested and inhaled antigens.
IgD is found on the surface of B cells (an immune system cell), and it likely helps B cells mature and function properly.
IgE is found in your skin, lungs, and mucus membranes; it protects against parasites and causes mast cells (a type of white blood cell) to react to allergens.
IgG, the most common antibody, is mostly found in blood and tissue fluids, and it protects against viral and bacterial infections (it’s also the only type of immunoglobulin that crosses the placenta and protects developing fetuses from infections).
IgM is found in the circulatory and lymphatic systems. It is the first line of defense against infections and plays a significant role in regulating immunity.
There are several different types of RF antibodies. The most common is IgM (immunoglobulin M), but IgA and IgG varieties are also sometimes found in tests for RF.
Rheumatoid arthritis arises when the immune system mistakenly attacks the joints, causing painful inflammation. It most often affects the joints of the hands, wrists, and knees.
The chronic inflammation of RA begins with the overproduction of autoantibodies — antibodies that attack the body’s own tissues — like RF and anticyclic citrullinated protein/peptide antibody (anti-CCP antibody or ACPA). It’s unclear what exactly causes these autoantibodies to develop, but it’s thought to involve a combination of genetics and environmental factors that affect various immune system cells.
The autoantibodies recruit the immune system’s pathogen-fighting white blood cells, which enter the synovium and cause inflammation. When this inflammation damages tissues, the body reacts by producing more antibodies, creating a positive feedback loop that leads to chronic inflammation.
The majority of people with RA have detectable RF in their blood, so RF is used as a biomarker or biological sign to help diagnose RA. That is, blood tests that detect high levels of the protein indicate you may have RA and need more tests. A positive result for an RF test cannot be used alone to diagnose RA, as RF is involved in other autoimmune conditions and some people with RA do not have RF in their blood.
While RF is closely linked to rheumatoid arthritis, it’s also present in other autoimmune conditions, such as:
Cryoglobulinemia, which causes abnormal clumps of protein to develop in the blood
Systemic lupus erythematosus (SLE), the most common type of lupus
Polymyositis, which involves chronic inflammation of certain muscles
Dermatomyositis, an inflammatory condition affecting the skin and muscles
Mixed connective tissue disease, which has signs and symptoms of at least two other connective tissue diseases, such as SLE, polymyositis, and dermatomyositis
Other non-autoimmune conditions can also elevate your RF levels, including:
Viral infections such as hepatitis C, HIV, and Epstein-Barr virus
Bacterial infections such as tuberculosis and endocarditis (infection of the heart valves)
Parasites
Sarcoidosis, which occurs when clumps of abnormal immune cells form in certain organs
Liver, lung, and kidney diseases
Certain cancers such as leukemia and multiple myeloma
Your RF levels may also be elevated simply because of advanced age (70-plus), even if you’re healthy.
Given the range of health issues that can cause an RF spike, RF tests can yield positive results in people who don’t have RA or other autoimmune diseases. To determine if you have RA, your doctor will also consider your symptoms and results of other tests, such as ACPA tests and imaging scans.
Your healthcare provider may order an RF blood test if they suspect you have RA or another autoimmune disease, such as if you have these signs and symptoms of RA:
Joint pain
Joint inflammation (tenderness, swelling, and warmth)
Joint stiffness, typically occurring first thing in the morning, that lasts longer than 30 minutes
Fatigue
The RF test involves a simple blood draw like any other blood test. This is typically conducted at a clinic, but at-home RF test kits — in which you prick your finger and mail the collected blood sample to a lab for analysis — are also available.
A positive (abnormal) test result means your body is producing higher-than-normal RF antibodies — more than 20 IU/mL (international units per milliliter). This result alone is not enough to diagnose you with RA or another autoimmune condition.
A negative (normal) result means your body produces RF at levels less than 20 IU/mL. You may still have RA if you receive a negative RF test result.
For RA, the RF test’s sensitivity (how well it correctly detects RA) varies widely between studies, ranging from 26 percent to 90 percent. One meta-analysis found an overall sensitivity of 69 percent, meaning that this percentage of people with RA will test positive for RF.
Similarly, the specificity of RF testing for RA (how well it avoids false positive results) varies, but it’s generally thought to be around 85 percent. This means the vast majority of the general population will test negative for RF, but 15 percent might test positive even though they don’t have RA.
Research also suggests that if your tests show really high levels of RF (more than three times the upper limit of normal), your likelihood of having RA increases. But if you have another inflammatory or rheumatic (affecting joints or other connective tissues) condition, your likelihood of receiving a false positive result increases. A test result showing a really low RF level does not automatically mean you do not have RA.
The RF test is just one part of an RA diagnosis, which will likely also involve tests to detect ACPA and inflammatory markers, as well as ultrasound or MRI (magnetic resonance imagery) scans to detect joint inflammation, erosion, and fluid buildup.
There are two subtypes of RA: seropositive and seronegative. Seropositive RA means that certain antibodies, like RF, have been found in blood tests. Seronegative RA may be diagnosed when test results don’t reveal RF or ACPA antibodies.
Generally, people with seropositive RA have a poorer prognosis. If you develop RF before any RA symptoms you may also have a poorer prognosis — the earlier the onset of RF, the more severe your disease may be. But most people without symptoms who test positive for RF do not go on to develop RA.
For those with seropositive RA, your RF levels may indicate how severe your disease is. High RF levels often predict more severe disease forms. You may be more likely to have non-joint symptoms, including those that affect the lungs and heart, and may experience more frequent flare-ups of symptoms.
Rheumatoid factor can guide treatment decisions, allowing for a personalized approach to RA management.
Additionally, your RF level may partially determine which drugs you receive for your treatment. A high RF level may indicate you are more likely to benefit from treatments that deplete immune system B cells, which release RF, such as rituximab. If you are RF positive versus RF negative, you may be less likely to respond well to a class of drugs called TNF-alpha inhibitors.
Talk to your doctor about the right treatment approach for you.
Rheumatoid factor is a valuable biomarker for understanding RA and other conditions.
While it’s an essential tool in diagnosing and managing autoimmune diseases, RF tests alone cannot definitively diagnose any condition, and results need to be taken in context of other symptoms and tests.
Elevated RF doesn’t confirm RA on its own, but it offers insight into disease severity and helps shape effective treatment strategies.
