Rheumatoid Factor

Diagnosing Rheumatoid Arthritis and Related Disorders

Mar 19, 2006 Elaine Moore

This article describes the rheumatoid factor (RF) test, and it explains how RF contributes to symptoms in rheumatoid arthritis and several other autimmune disorders.

Rheumatoid factor (RF) is a term used to describe a group of autoantibodies known as rheumatoid factors. The RF test is considered the basic screen and hallmark for the autoimmune disorder rheumatoid arthritis (RA). RF is considered an early marker since its presence is associated with an increased risk of developing RA in people with mild arthritic symptoms.

RF factors include three subclasses that react with the crystallizable fragment (Fc fragment) of immunoglobulin G (IgG). Immunoglobulins are proteins normally found in the body that are used to produce antibodies. IgG is a subclass of immunoglobulin with a structure allowing it persist for a long time. IgG antibodies produced in response to infection or vaccines generally persist for life. RF targets these proteins by combining with them to form deposits that lodge into joints and tissues.

RF is not only present in patients with rheumatoid arthritis. It may also occur in patients with other autoimmune conditions such as systemic lupus erythematosus (SLE), Sjogren's syndrome, and occasionally scleroderma and polymyositis. It is also seen in the rheumatoid arthritis overlap syndromes, such as RA/SLE overlap and Scleroderma/RA overlap. Like the ANA test, the RF test may also be positive in other conditions and in the absence of disease, especially with advancing age. Other conditions that may cause a positive RF test result include chronic active hepatitis, sarcoidosis, chronic infection, various cancers and syphilis.

The three subclasses of RF include IgM, IgA and IgG autoantibodies. Most tests for RF measure each of these subtypes. Each subtype is associated with a different symptom or disease process, and the simultaneous presence of all three types is usually only seen in rheumatoid arthritis. RF, type IgA antibodies, are associated with symptoms other than those affecting joints, such as mucosal and secretory problems and bone erosions. In patients with rheumatoid arthritis, IgM RF predominates and the other subtypes are usually present in lower amounts.

Rheumatoid factors are found in 50-90 percent of patients with classic RA, with higher concentrations seen in active disease. Higher titers are also seen in more severe forms of the disease. RF are also seen in 75-95 percent of patients with Sjogren's syndrome, 50-60 percent of patients with mixed connective tissue disease (MCTD), 25-40 percent of patients with the kidney disease IgA nephropathy, 15-35 percent of patients with SLE, 20-30 percent of patients with systemic sclerosis and 5-10 percent of patients with polymyositis and dermatomyositis.

The disease process in rheumatoid arthritis involves the presence of deposits of RF complexed or linked with IgG occurring in various tissues, such as the synovium or joints. These complexes interfere with the normal function of the joint and promote inflammation. The inflammation and the effects of immune system chemicals result in tissue damage and sometimes damage to blood vessels in the affected area. The RF test is used to diagnose arthritic conditions and to monitor response to treatment and prognosis. During periods of remission or a favorable response to treatment, RF titers fall and the RF test results may be negative.

Resource: Marc Golightly and Candace Golightly, Laboratory Diagnosis of Autoimmune Disease, Medical Laboratory Observer, July, 2002.

James Peter and Herminio Reyes, Use and Interpretation of Tests in Rheumatology, Santa Monica, CA: Specialty Laboratories 1996.

The copyright of the article Rheumatoid Factor in General Medicine is owned by Elaine Moore. Permission to republish Rheumatoid Factor in print or online must be granted by the author in writing.

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May 13, 2008 7:43 AM

Guest :

Hi Elaine,

I just wanted to point out that Immunoglobulins are not proteins that help produce antibodies. Immunoglobulins are antibodies and they are produced by B-cells.

Nov 23, 2008 9:03 PM

Guest :

Below: Not all immunoglobulins are antibodies (they can be B cell receptors). In a way, Immunoglobulin function can be described as proteins that help produce antibodies: The membrane proteins, B-cell receptors, are immunoglobulins that serve as a receptor for a specific antigen and the specific antibodies that are secreted by B-cells mimic the specificity of the membrane-bound immunoglobulin. So, while it is not technically the Ig that secretes the antibodies, the Ig plays a role in the formation of antibodies secreted by the B cell. So Elaine isn't really wrong. And Igs are absolutely proteins.

Nov 23, 2008 9:03 PM

Guest :

Below: Not all immunoglobulins are antibodies (they can be B cell receptors). In a way, Immunoglobulin function can be described as proteins that help produce antibodies: The membrane proteins, B-cell receptors, are immunoglobulins that serve as a receptor for a specific antigen and the specific antibodies that are secreted by B-cells mimic the specificity of the membrane-bound immunoglobulin. So, while it is not technically the Ig that secretes the antibodies, the Ig plays a role in the formation of antibodies secreted by the B cell. So Elaine isn't really wrong. And Igs are absolutely proteins.

Dec 11, 2008 7:55 AM

Guest :

Hi,
When you get a RF test done what is the test results for a - to a + test results.
5 be - and 20 being +.
With a higher number does that mean your rheumatiod is worse?

Dec 11, 2008 11:05 AM

Elaine Moore :

Hi,
A higher titer doesn't necessarily mean that your disease is more severe. The titer is generally higher during active disease flares and lower during periods when you're in remission or showing a good response to therapy. Best, Elaine

Dec 18, 2008 7:41 AM

Guest :

Hi. I have had two RF tests (along with Sed Rate and CRP) and they are all increasing. In 2/2008 RF was 108.0IU/mL and now (12/2008) it is 711.4. I don't have any infections, etc. I have osteoarthritis in my back, knees, etc. I'll be 40 next year and I'm just starting to keep track of lab results, etc. for myself.

The doctor says not to worry about the results, they don't mean anything. Is that correct? I just don't want to be one of those "if only we'd known sooner" people.

Thanks much. Happy Holidays.

Dec 18, 2008 10:45 AM

Elaine Moore :

Hi,
Do both tests use the same reference ranges. It could be that the lab is using a new testing method that's more sensitive. Typically, the ranges differ when new methods are introduced.
In general, the RF titer rises during flares and falls, often to normal, when patients are responding well to medications. Could you have been on a med before that was helping.
I'd ask to have the CCP test for citrillinated peptide antibodies since it's much more specific for rheumatoid arthritis. It's described at rheumatism.suite101.com/article.cfm/rheumatoid_arthritis_today

Best, elaine

Dec 18, 2008 12:50 PM

Guest :

Thanks, Elaine.

They are using the same test and reference range - at least that's what they told me. :)

I don't take anything for my osteoarthritis, other than aspirin and have been on the same meds for other conditions for well over a year with no changes in doses, etc. I have been put on Vitamins B-12 and D, as well as selenium (my hypothyroid is all over the place) since July. Perhaps those affect the outcomes.

I'll see if I can get the CCP. My doctor kind of rolls his eyes when I try to do this keeping-track-for-myself stuff, but I don't expect the doctor to keep up on everything that I am concerned about. I say that now that I'm turning 40, I'm taking charge of my health care and they can just follow along. I'm not a hypochondriac by any stretch of the imagination, but I'm done with being just a bystander in what happens to me. Look out - I'm getting old and cranky! LOL

I'm stiff and sore in the morning and sore most days. I did a lot of damage to myself with sports and grunt labor, so I just assume that I'm paying for all of that now. I have had a couple of bouts of horrible pain (shoulder, then hand) that did not come from injury or overuse. Those lasted several days each and then just went away. My hand felt like it was broken, but it wasn't. I'm just trying to keep a calendar of things and a chart of test results for future reference.

I hope to not develop RA, obviously. It sounds like such a painful and futile disease. Best wishes to anyone dealing with that. Thanks for listening. Cheers.

Jan 12, 2009 4:54 AM

Guest :

I am a 48 year old female. I developed severe shoulder and hand pain and stiffness, worse in the morning, but it even wakes me up at night. My RF was 41. Can anyone tells me what this means?

Jan 12, 2009 1:13 PM

Elaine Moore :

Hi,
You'll want to look at the reference range used by the lab that ran the test to tell if your result is considered positive or negative. For instance, if the reference or normal range is 1-10, your result would be positive. If your result is actually a titer of 1:40 and the reference range is up to 1:40 your result would be considered borderline.
See this link http://www.labtestsonline.org/understanding/analytes/rheumatoid/test.htmlfor more information.
The RF is positive during flares of certain autoimmune disorders including rheumatoid arthritis and other conditions. Best, Elaine

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