Rheumatoid Factor in Rheumatoid Arthritis and Related Disorders

By Elaine Moore

Rheumatoid factor (RF) is an autoantibody found in the blood of individuals with rheumatoid arthritis and other autoimmune connective tissue disorders.

Rheumatoid factor (RF) is an abnormal protein substance that occurs as an autoantibody in certain autoimmune disorders. Its presence in the blood serves as a marker of various diseases.

Blood tests for rheumatoid factor detect the presence of antibodies that belong to a family 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. However, because RF is not specific for RA and it may not show up (as a positive blood test result) in inactive disease states, a better test for diagnosing rheumatoid arthritis is the blood test for cyclic citrillinated peptide or CCP.

The Rheumatoid Factor Group

RF factors include three subclasses of protein antibodies 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 are produced in response to infection or vaccines or to the body’s own proteins in autoimmune disease. IgG antibodies and autoantibodies generally persist for life. The RF antibody targets these IgG proteins and combines with them to form deposits that lodge into joints and tissues in connective tissue disorders.

In doing so, rheumatoid factor causes symptoms of arthritis and it serves as a disease marker. The presence of RF in blood specimens indicates that the patient has an autoimmune connective tissue disorder. Further blood tests including tests for antinuclear antibodies are used to determine the specific connective tissue disorder that’s present.

Conditions are Associated with RF

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. Similar to the ANA test, the RF test may also be positive in other non-arthritic 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. Conditions of arthritis in which the RF is repeatedly negative are referred to as seronegative arthritis.

Subclasses of RF

Although RF targets IgG immunoglobulins, RF antibodies may occur as other antibody subclasses. The three subclasses of RF include IgM, IgA and IgG autoantibodies. Most blood 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.

Disease Process in Rheumatoid Arthritis

The disease process in rheumatoid arthritis involves the presence of deposits of RF complexed or linked with IgG that lodge in various tissues, such as the synovium or joints. These complexes of RF with IgG interfere with the normal function of the joint and promote inflammation. The inflammation and the effects of immune system chemicals, particularly pro-inflammatory cytokines, result in tissue damage and sometimes damage to blood vessels located in the affected area.

The RF test can be used to diagnose arthritic conditions and also to monitor response to treatment as well as prognosis. During periods of remission or during a favorable response to treatment, RF titers fall and the RF test results may be negative. During disease flares and symptom exacerbations, the RF titer in these conditions rises. To assess treatment response, tests for inflammatory markers such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are also ran, with increased levels indicating increased inflammation. ♦

© 16 Nov 2010 by Elaine Moore

Resources:

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: Nichols Laboratory.