Introduction
Rheumatoid factors are a type of immunoglobulin (Ig) that was initially discovered about 70 years ago. Rose first identified specific antibodies among rheumatoid arthritis (RA) patients in 1948, and they were termed rheumatoid factors in 1952 because of their relationship to the disease. Although they were first discovered in RA patients, RFs can also be detected in patients with various autoimmune and non-autoimmune disorders, as well as healthy people. Antibodies targeting the Fc region of immunoglobulin G, known as rheumatoid factors, come in a variety of isotypes and affinities. Whereas other immunoglobulin types, such as IgG and IgA, were hardly seen. The most prevalent RF is IgM.
What Are the Functions of Rheumatoid Factor?
Without immunogenic stimulation, rheumatoid factors are not detectable in circulation. They are thought to be a natural reaction to a range of antigenic stimuli, such as toxic compounds like lipopolysaccharides or pathogens like the Epstein–Barr virus (EBV). They produce immunological complexes, which are then phagocytosed by inflammatory cells. These RFs are transitory, low-affinity polyclonal antibodies produced by the germ cells. In this situation, their position could be termed protective.
Fig 1: Role of rheumatoid factor in rheumatoid arthritis
A complicated interaction between B - lymphocytes, T - lymphocytes, and dendritic cells are involved in the pathophysiology of RA. Loss of tolerance to citrulline-containing proteins is caused by a variety of environmental and genetic causes, resulting in the formation of autoantibodies such as anti-cyclic citrullinated protein antibody (ACPA) and RF. It is probable that this antigenic input also triggers the synthesis of RF that produces B cells, which perform isotype switching and keep the inflammatory reaction continuing. Additional activation and adhesion of inflammatory cells such as macrophages, neutrophils, and lymphocytes may result from the involvement of RF in the complex immune development. This causes tissue damage and creates a positive feedback loop in which more autoantibodies are produced. An autoimmune and self-sustaining inflammatory response, which eventually leads to arthritis, could be explained by such a mechanism.
What Disorders Are Associated With High Rheumatoid Factor Levels?
Chronic and persistent immune system stimulation leads to chronic inflammation. These autoantibodies often vanish after successful therapy of the underlying illness. Hepatitis C may have a high concentration of RFs (as high as 76 percent ). This is especially true in situations of cryoglobulinemia, which is most commonly associated with hepatitis C but can also occur in the absence of hepatitis C. The reason for this is that cryoglobulins are cold precipitating IgM antibodies against IgG, which is also the basic description of a rheumatoid factor. It has been proposed that all patients with elevated RF levels have their HCV status tested.
What Is the Test for Rheumatoid Factor?
The concentration of the rheumatoid factor (RF) in the blood is measured by the rheumatoid factor (RF) test. Rheumatoid arthritis is commonly diagnosed via an RF test. Rheumatoid factors can also indicate the presence of other autoimmune diseases, such as juvenile arthritis, infections, and cancer. This test is done by collecting a little sample of blood from a vein in your arm during a rheumatoid factor test. This usually only takes a few minutes. A sample of blood is submitted to a laboratory for testing.
When to Do Rheumatoid Factor Test?
A rheumatoid factor test can be done when the patient has symptoms like pain in the joints, early morning stiffness of the joints, swelling in the joints, generalized weakness, and a mild increase in temperature.
What Is the Clinical Significance of Rheumatoid Factor?
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The presence or absence of rheumatoid factors, as well as their titers and isotypes, have outstanding value for the diagnosis and prognosis of rheumatoid arthritis. Seropositive RA patients may have severe and erosive joint disease and extra-articular symptoms like rheumatoid nodules and vasculitis than seronegative patients.
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Similarly, high RF titers increase the chances of a patient developing RA and, consequently, a worse prognosis. Furthermore, RF appears at different times in RA patients. Some people get RF before they develop clinical illness.
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The emergence of RF early in these patients has been related to a more severe illness. Most asymptomatic people with a positive RF, on the other hand, do not develop RA. However, there is a group of patients who develop RF after experiencing symptoms. The mechanism that causes this variation is unknown.
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The sensitivity and specificity of RF testing in RA patients have been found to be 60 to 90 percent and 85 percent, respectively. The sensitivity could range from 26 percent to 90 percent, depending on the subject and control group used. ACPA testing has been added to the RA classifications to improve specificity. For early rheumatoid arthritis, ACPA offers higher specificity than RF; therefore, the positivity for both ACPA and RF, in addition to clinical manifestations, provides more sensitivity and aids in diagnosis.
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RFs have limited clinical usefulness in predicting RA prognosis and therapy response. It is currently not suggested to use RF monitoring just to track RA disease activity. However, it may have a role in predicting the therapeutic efficacy of some therapeutic drugs. Increased pretreatment levels of RF, for example, have been linked to a poor therapeutic outcome of TNF-alpha medications, and seropositive RA patients have a stronger response to Rituximab than seronegative RA patients.
Conclusion
Patients with arthritis/arthralgia should not be tested for RFs unless there is a high clinical suspicion of RA. But if the individual has already been confirmed with RA, consultation with a rheumatologist is recommended. Rheumatologists who are involved early in the management of RA patients had better outcomes of normal function and disability of the joint. To achieve a positive illness outcome, the general practitioner and the rheumatologist must work together.
