By Lana Bandoim 

 Medically reviewed by David Ozeri, MD

Rheumatoid arthritis (RA) can be difficult to diagnose because no single test can prove you have it. Because of this, diagnoses are based on several factors.

In addition to getting your medical history and doing a physical exam, your healthcare provider will also order several imaging and blood tests to determine whether you have the condition.1

The blood tests can show if your body has inflammation and is making specific proteins (antibodies) that are common when you have RA.1

The blood tests may include:

• Rheumatoid factor (RF)

• Anti-cyclic citrullinated peptide (Anti-CCP)

• Erythrocyte sedimentation rate (ESR)

• C-reactive protein (CRP)

• Antinuclear antibody (ANA)

• Complete blood count (CBC)

What Is Rheumatoid Arthritis?

Similar to other autoimmune conditions, rheumatoid arthritis causes your immune system to attack the healthy tissues and cells in your body. Although RA usually damages the joints, it can affect other parts of the body, such as the eyes, heart, or lungs. RA can cause inflammation (swelling) in joints located in the wrists, hands, knees, and ankles.2

Symptoms can vary from person to person, but some early signs of RA include pain and tenderness in the joints. Over time, symptoms may get worse and progress to redness, stiffness, and swelling in the joints. Some people also have a low-grade fever and fatigue.1

The exact cause of RA is not known, but several factors increase the risk of having this disease. It occurs more often in older adults and women. Smoking and being overweight also raise the risk of having RA. Certain genes have been linked to a higher chance of developing RA.2 

Illustration by Verywell

Rheumatoid Factor (RF)

Rheumatoid factor (RF) is an antibody, which is a type of blood protein your immune system makes. Rheumatoid factor Rheumatoid factor is part of the immune system’s attack on healthy tissues and cells in the body that causes inflammation. It is possible to measure RF with a blood test.3

Since about 80% of adults with RA have rheumatoid factor, it is a common blood test during the diagnosis process. However, the RF blood test on its own is not enough to make a diagnosis because you may have RA without RF in your blood. In addition, some people have a positive RF blood test because of other conditions and not RA.3

You do not need to make any special preparations before the blood test. During the RF blood test, a healthcare professional will collect blood from your vein and put it in a test tube. A laboratory will test your blood to check for the presence of rheumatoid factor. The blood test is a low-risk procedure that should not have any serious side effects.4  

Interpreting Results

A positive RF blood test means that you have rheumatoid factor in your body. This indicates that you may have RA or another autoimmune condition.

A positive RF blood test is not a definitive diagnosis for RA. A negative RF blood test does not automatically mean you do not have RA. Some people with RA have negative RF blood tests. Your healthcare provider will order more tests before diagnosing RA.3

Anti-Cyclic Citrullinated Peptide (Anti-CCP)

Anti-cyclic citrullinated peptide (anti-CCP) is a type of antibody found in the blood that can be measured with a blood test. Its other names include citrulline antibody, cyclic citrullinated peptide antibody, anticitrullinated peptide antibody, and ACPA. Similar to rheumatoid factor, anti-CCP is part of the immune system's attack on healthy cells in the body that causes inflammation.5

About 75% of adults with RA have anti-cyclic citrullinated peptides in their blood. It is rare for a person without RA to have anti-CCP. Your healthcare provider may order the anti-CCP test along with the rheumatoid factor blood test during the RA diagnosis process. If you test positive for both antibodies, there is a strong chance you have RA.5

A healthcare professional will collect your blood from your vein during an anti-CCP blood test. The blood sample will go to a laboratory, which will check for the presence of anti-cyclic citrullinated peptide. The anti-CCP blood test is a low-risk procedure that does not have any side effects.5

Interpreting Results

A positive anti-cyclic citrullinated peptide blood test means you have these antibodies in your blood and may have RA. A negative anti-CCP blood test means you do not have the antibodies, but you may still have RA.5

A positive anti-CCP and positive RF blood test indicate there is a strong chance you have RA. A positive anti-CCP and negative RF blood test show that you may be in the early stages of the disease or may have it in the future. A negative anti-CCP and negative RF blood test mean you may not have RA, so your healthcare provider may order more tests.5

Erythrocyte Sedimentation Rate (ESR)

Erythrocytes are red blood cells. An erythrocyte sedimentation rate (ESR) is a blood test that measures how fast the red blood cells settle to the bottom of a test tube. If the red blood cells settle quickly, then you may have inflammation in your body. Inflammation can make erythrocytes clump together, which makes it easier for them to settle in a test tube.6

Other names for this test include SED rate and Westergren sedimentation rate. An ESR blood test can show if you have inflammation, which may be caused by an autoimmune condition like RA. However, an erythrocyte sedimentation rate does not provide a definitive diagnosis for RA because other conditions can cause inflammation in the body.6

You do not need to do anything special to prepare for the blood test. When you have an ESR blood test, your blood will be collected from a vein and placed in a test tube. A laboratory will measure the erythrocyte sedimentation rate.6

Interpreting Results

An ESR test cannot diagnose a specific disease. It can only show if there is inflammation in your body.

A high erythrocyte sedimentation range means that there is more inflammation in your body, and you may have an autoimmune condition, infection, or cancer. A moderately increased ESR can be observed with anemia, infection, menstruation, or pregnancy. A normal ESR helps exclude inflammation, particularly chronic inflammation.6

If you have a high or moderate ESR blood test result, then your healthcare provider may order additional tests to check for RA. The ESR test is rarely done on its own to diagnose RA.6

C-Reactive Protein (CRP)

Your liver makes C-reactive protein (CRP). The levels of CRP increase when there is inflammation in your body. It is possible to measure CRP levels with a blood test. Similar to the ESR test, CRP cannot definitively diagnose RA or another autoimmune condition. Instead, healthcare providers use these tests to determine if there is inflammation in the body and if additional testing is necessary.7

During the CRP test, your blood will be collected from a vein, so it can be analyzed. You do not need to make any special preparations prior to the test. It is a low-risk procedure without side effects.7

Interpreting Results

A high C-reactive protein blood test shows that you have inflammation in the body. A low CRP blood means it is less likely there is inflammation in the body.

Even if you have a high CRP test result, this does not automatically mean you have RA. You may have an infection or another inflammatory disease. Being overweight, smoking, and not exercising can also lead to high C-reactive protein levels. Your healthcare provider will order more tests if the results are positive.7

Antinuclear Antibody (ANA)

An antinuclear antibody (ANA) is a protein that your immune system makes. It is called antinuclear because it attacks the nucleus (center) of a cell. Antinuclear antibodies can damage healthy tissues and cells in the body. An ANA test measures the antinuclear antibodies in your blood to determine if you have an autoimmune disorder.8

The antinuclear antibody blood test cannot show if you have a specific disease, like RA. However, healthcare providers often order the ANA test to investigate other autoimmune diseases that can cause arthritis, for example, lupus. It is a step toward diagnosis.8

You do not need to prepare for an ANA test. During the test, a healthcare provider will collect blood from your vein, so it can be analyzed in a lab.8

Interpreting Results

A positive ANA test means you have antinuclear antibodies in your body. A negative ANA test indicates that you do not have these antibodies. A positive test is not a definitive diagnosis of RA. You may have another autoimmune condition or an infection that causes the positive results. Your healthcare provider will order other tests before diagnosing RA.8

Complete Blood Count (CBC) 

A complete blood count (CBC) is a test that looks at all the different cell types in your blood. Your healthcare provider may order a CBC test with differential and platelet counts during the RA diagnosis process to see if there is inflammation or other problems.9

A CBC test can measure your:

• White blood cells

• Red blood cells

• Hematocrit (percentage of red blood cells in your blood)

• Hemoglobin (protein in red blood cells that carries oxygen)

• Platelets (cell fragments that help with clotting) 

Blood will be collected from your vein during a CBC test. The sample will go to a laboratory for testing. A CBC test does not give a definitive diagnosis for RA.9

Interpreting Results

A CBC test will show the measurements of the different blood components, but not all of them are relevant for RA. Low white blood cell counts can indicate an autoimmune condition, cancer, or bone marrow problems. High white blood cell counts can mean you have an infection or inflammation.

A high white blood cell count can indicate you may have a condition like RA, but it is not a definitive diagnosis. Your healthcare provider will request other tests.9

Other Tests 

Your healthcare provider may also order imaging tests during the diagnosis process to check your joints. You may have an X-ray, magnetic resonance imaging (MRI), or ultrasound scans to look for damage in your joints. After diagnosis, you may continue to have imaging tests to check if treatment is working and to see how the disease is progressing.1 

To rule out the possibility of other autoimmune conditions, you may have additional tests. Your healthcare provider may also want to check for other diseases because of your symptoms or medical history. 

Tests may include: 

• Serum uric acid levels to rule out gout 

• Serologic testing (antibody testing) for human parvovirus B19, hepatitis B virus (HBV), hepatitis C virus (HCV), and Lyme disease

• Comprehensive metabolic panel to check your glucose, liver, and kidney function 

• HLA typing (genetic test) to check for the risk of having RA-like conditions

• Creatine kinase (CK) test to check for muscle damage 

• Complement blood test to measure complement proteins in the blood associated with autoimmune diseases

• Cryoglobulin test to check for abnormal proteins in the blood 

What to Expect During the Tests

You usually do not need to do anything before a blood test for RA, fasting is not required. Tell your healthcare provider if you are taking any prescription or over-the-counter medications that may affect your tests. 

Wear a garment that allows access to your elbow area for the blood draw. Bring your identification. The healthcare professional drawing the blood will ensure your identification and label the blood draw sample tubes.

A tourniquet will be placed on your arm, the vein area sanitized, and a needle will be used to collect the blood into one or more vials.

After drawing the blood, the site will be bandaged. You should not have any side effects and usually do not need to take any precautions after the test.

These tests are sent to the lab rather than being done in the clinic as a rapid test. Your results will not be available immediately but will be reported to your healthcare provider in hours to a day or more.

Rheumatoid Arthritis Diagnosis

There is not one blood test that can provide a definitive diagnosis for RA. This is why your healthcare provider will order multiple tests and also check your symptoms and medical history. Usually, a combination of positive tests that show inflammation and antibodies associated with RA can help your healthcare provider reach a diagnosis. 

Sources

Arthritis Foundation. Rheumatoid Arthritis: Causes, Symptoms, Treatments and More.

Centers for Disease Control and Prevention. Rheumatoid arthritis (RA).

Rheumatoid Arthritis Support Network. RF test: What is the normal range for a rheumatoid factor test?

U.S. National Library of Medicine: MedlinePlus. Rheumatoid factor (RF) test.

U.S. National Library of Medicine: MedlinePlus. CCP antibody test.

U.S. National Library of Medicine: MedlinePlus. Erythrocyte sedimentation rate (ESR).

U.S. National Library of Medicine: MedlinePlus. C-reactive protein (CRP) test.

U.S. National Library of Medicine: MedlinePlus. ANA (antinuclear antibody) test.

U.S. National Library of Medicine: MedlinePlus. Complete blood count (CBC).

By Lana Bandoim
Lana Bandoim is a science writer and editor with more than a decade of experience covering complex health topics.