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Rheumatoid factor (RF) is the
autoantibody An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies. ...
that was first found in
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are inv ...
. It is defined as an
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of t ...
against the Fc portion of
IgG Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG an ...
and different RFs can recognize different parts of the IgG-Fc. RF and IgG join to form
immune complex An immune complex, sometimes called an antigen-antibody complex or antigen-bound antibody, is a molecule formed from the binding of multiple antigens to antibodies. The bound antigen and antibody act as a unitary object, effectively an antigen o ...
es that contribute to the
disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
process. Rheumatoid factor can also be a cryoglobulin (antibody that precipitates on cooling of a blood sample); it can be either type 2 (monoclonal IgM to polyclonal IgG) or type 3 (polyclonal IgM to polyclonal IgG) cryoglobulin. Although ''predominantly'' encountered as IgM, rheumatoid factor can be of any isotype of immunoglobulins, i.e. IgA, IgG, IgM, IgE, IgD.


Testing

RF is tested by collecting blood in a plain tube (5 mL is often enough). The serum is tested for the presence of RF. There are different methods available, which include nephelometry, turbidimetry, agglutination of gamma globulin-coated latex particles or erythrocytes. RF is often evaluated in patients suspected of having any form of arthritis even though positive results can be due to other causes, and negative results do not rule out disease. But, in combination with signs and symptoms, it can play a role in both diagnosis and disease prognosis. It is part of the usual disease criteria of
rheumatoid Rheumatism or rheumatic disorders are conditions causing chronic, often intermittent pain affecting the joints or connective tissue. Rheumatism does not designate any specific disorder, but covers at least 200 different conditions, including art ...
arthritis. The presence of rheumatoid factor in serum can also indicate the occurrence of suspected autoimmune activity unrelated to rheumatoid arthritis, such as that associated with tissue or organ rejection. In such instances, RF may serve as one of several serological markers for autoimmunity. The sensitivity of RF for established rheumatoid arthritis is only 60-70% with a specificity of 78%. Rheumatoid factor is part of the 2010 ACR/EULAR classification criteria for
Rheumatoid Arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are inv ...
. RF positivity combines well with anti-CCP and/or 14-3-3η ( YWHAH) to inform diagnosis. RF positivity at baseline has also been described as a good prognostic marker for future radiographic damage.


Interpretation

High levels of rheumatoid factor (in general, above 20 IU/mL, 1:40, or over the 95th
percentile In statistics, a ''k''-th percentile (percentile score or centile) is a score ''below which'' a given percentage ''k'' of scores in its frequency distribution falls (exclusive definition) or a score ''at or below which'' a given percentage fall ...
; there is some variation among labs) occur in rheumatoid arthritis (present in 80%) and Sjögren's syndrome (present in 70%).Rheumatoid Factor - Patient UK
/ref> The higher the level of RF the greater the probability of destructive articular disease. It is also found in
Epstein–Barr virus The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. It is ...
or Parvovirus infection and in 5 to 10% of healthy persons, especially the elderly. There is an association between rheumatoid factor and more persistently active synovitis, more joint damage, greater eventual disability and arthritis. Other than in
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are inv ...
, rheumatoid factor may also be elevated in other conditions, including: * Systemic lupus erythematosus (SLE) * Sjögren syndrome * Hepatitis B and C, herpes, HIV, and other viral infections * Primary biliary cirrhosis * Infectious mononucleosis and any chronic viral infection *
Leprosy Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria '' Mycobacterium leprae'' or '' Mycobacterium lepromatosis''. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve d ...
*
Sarcoidosis Sarcoidosis (also known as ''Besnier-Boeck-Schaumann disease'') is a disease involving abnormal collections of inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph nodes. Less commonly af ...
*
Tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, ...
,
Syphilis Syphilis () is a sexually transmitted infection caused by the bacterium '' Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, a ...
and other chronic bacterial infections *
Visceral leishmaniasis Visceral leishmaniasis (VL), also known as kala-azar ( Hindi: kālā āzār, "black sickness") or "black fever", is the most severe form of leishmaniasis and, without proper diagnosis and treatment, is associated with high fatality. Leishmanias ...
*
Malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. ...
and other parasitic infections *
Cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...


History

The test was first described by Norwegian Dr
Erik Waaler Erik Waaler (22 February 1903 – 3 March 1997) was a Norwegian professor of medicine. He was born in Hamar as a son of physician Per Waaler (1866–1923) and musician Fredrikke Waaler, Fredrikke Amalie Holtemann Rynning (1865–1952). He was a b ...
in 1940 and redescribed by Dr Harry M. Rose and colleagues in 1948. Redescription is said to be due to the uncertainties due to World War II. It is still referred to as the Waaler-Rose test.


References


External links


RF
on MedlinePlus

on Lab Tests Online *
Rheumatoid Factor
on WebMD {{DEFAULTSORT:Rheumatoid Factor Autoantibodies Rheumatology