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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. Pr ...
that was first found in
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...
. It is defined as an
antibody An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...
against the Fc portion of IgG 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 of ...
es that contribute to the
disease A disease is a particular abnormal condition that adversely affects the structure or function (biology), function of all or part of an organism and is not immediately due to any external injury. Diseases are often known to be medical condi ...
process such as chronic inflammation and joint destruction at the synovium and
cartilage Cartilage is a resilient and smooth type of connective tissue. Semi-transparent and non-porous, it is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints ...
. 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 A nephelometer or aerosol photometer is an instrument for measuring the concentration of suspension (chemistry), suspended particulates in a liquid or gas colloid. A nephelometer measures suspended particulates by employing a light beam (source b ...
, turbidimetry, agglutination of gamma globulin-coated latex particles or
erythrocyte Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood ce ...
s. RF is often evaluated in patients suspected of having any form of
arthritis Arthritis is a general medical term used to describe a disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, Joint effusion, swelling, and decreased range of motion of ...
, even though positive results can be due to other causes and negative results do not rule out disease. In combination with signs and
symptom Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...
s, it can play a role in both diagnosis and disease
prognosis Prognosis ( Greek: πρόγνωσις "fore-knowing, foreseeing"; : prognoses) is a medical term for predicting the likelihood or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) ...
. It is part of the usual disease criteria of
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...
. 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 Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mi ...
markers for autoimmunity. The sensitivity of RF for established rheumatoid arthritis is only 60 to 70 percent with a specificity of 78 percent. Rheumatoid factor is part of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis. RF positivity combines well with anti-CCP and/or 14-3-3η (
YWHAH 14-3-3 protein eta also referred to as 14-3-3η is a protein that in humans is encoded by the ''YWHAH'' gene. Function This gene product belongs to the 14-3-3 family of proteins that are normally intracellular in nature and help to mediate si ...
) 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, also known as percentile score or centile, is a score (e.g., a data point) a given percentage ''k'' of all scores in its frequency distribution exists ("exclusive" definition) or a score a given percentage ...
; there is some variation among labs) occur in rheumatoid arthritis (present in 80%) and Sjögren's syndrome (present in 50-70% of primary forms of disease).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), also known as human herpesvirus 4 (HHV-4), is one of the nine known Herpesviridae#Human herpesvirus types, human herpesvirus types in the Herpesviridae, herpes family, and is one of the most common viruses in ...
or Parvovirus infection and in 5–10% 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 Arthritis is a general medical term used to describe a disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, Joint effusion, swelling, and decreased range of motion of ...
. Other than in
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...
, rheumatoid factor may also be elevated in other conditions, including: *
Systemic lupus erythematosus Lupus, formally called systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common ...
(SLE) * Sjögren syndrome *
Hepatitis B Hepatitis B is an infectious disease caused by the '' hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. ...
and C,
herpes Herpes simplex, often known simply as herpes, is a viral infection caused by the herpes simplex virus. Herpes infections are categorized by the area of the body that is infected. The two major types of herpes are oral herpes and genital herp ...
, HIV, and other viral infections *
Primary biliary cirrhosis Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to buil ...
*
Infectious mononucleosis Infectious mononucleosis (IM, mono), also known as glandular fever, is an infection usually caused by the Epstein–Barr virus (EBV). Most people are infected by the virus as children, when the disease produces few or no symptoms. In young adu ...
and any chronic viral infection *
Leprosy Leprosy, also known as Hansen's disease (HD), is a Chronic condition, long-term infection by the bacteria ''Mycobacterium leprae'' or ''Mycobacterium lepromatosis''. Infection can lead to damage of the Peripheral nervous system, nerves, respir ...
*
Sarcoidosis Sarcoidosis (; also known as Besnier–Boeck–Schaumann disease) is a disease involving abnormal collections of White blood cell, inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph n ...
*
Tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...
,
syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms depend on the stage it presents: primary, secondary, latent syphilis, latent or tertiary. The prim ...
and other chronic bacterial infections * Visceral leishmaniasis *
Malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
and other parasitic infections *
Cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...


History

The test was first described by Norwegian Dr Erik Waaler 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