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Rheumatoid factor (RF) is a specific antibody raised against the antigenic determinant cluster of the Fc fragment of human or animal immunoglobulin. It is also an autoantibody with denatured IgG as the target antigen, and is therefore also called an anti-antibody. Rheumatoid factor is found in the serum and synovial fluid of patients with rheumatoid arthritis and certain autoimmune diseases. B-cell clones that produce rheumatoid factor are found in patients with rheumatoid arthritis and in about 50% of healthy people. Under the direct action of denatured IgG or Epstein-Barr virus, rheumatoid factor can be synthesized in large quantities. Healthy people have fewer cell clones that produce rheumatoid factor, and the soluble factors secreted by monocytes can inhibit rheumatoid factor production, making it generally difficult to detect. Rheumatoid factor has two biological actions. Under certain circumstances, rheumatoid factor can protect the body by improving the body's clearance of circulating immune complexes. On the other hand, rheumatoid factor combines with denatured IgG in the body to form immune complexes, activates complement, or is phagocytosed by phagocytes, which release lysosomal enzymes, active peptides, collagenase, prostaglandin E, etc., causing joint damage or vasculitis.
Figure 1. Rheumatoid factor IgM autoantibodies control IgG homeostasis.(Sources: Nicolò A, et al. 2022)
Rheumatoid factor is a group of autoantibodies that can recognize the FC segment of denatured immunoglobulin IgG and includes three main subtypes: IgM-RF, IgG-RF and IgA-RF. 1) IgM type RF: When the IgM type RF titer in the serum of Rheumatoid arthritis (RA) patients is >80 IU/ml and accompanied by severe joint dysfunction, it usually indicates a poor prognosis for the patient. 2) IgG type RF: The presence of IgG type RF in the serum or synovial fluid of RA patients is closely related to the patient's synovitis, vasculitis and joint symptoms. 3) IgA type RF: This is an indicator of the clinical activity of RA. IgA type RF positivity is significantly related to the severity of arthritis symptoms and bone destruction in patients. The positive rate of RF in RA is as high as 75%, but its specificity is poor. It has also been detected in other autoimmune diseases such as systemic lupus erythematosus, Sjögren's syndrome, various infectious diseases and even in the serum of normal people (positive in healthy people). The rate is 3%~5%10%~30% in the elderly). A negative RF test cannot rule out RA, and a positive test must be combined with clinical symptoms for diagnosis. Because the rheumatoid factor assay has high sensitivity but low specificity, it can be positive in many connective tissue diseases, especially in patients with Sjögren's syndrome, who often have high titer rheumatoid factor positivity. In some non-connective tissue diseases, such as infections, tumors and other diseases, even normal people have a certain positive rate. Therefore, it is not possible to judge whether a patient has rheumatoid arthritis based on rheumatoid factor positivity alone.
Studies have shown that a rheumatoid factor level exceeding a certain titer is called rheumatoid factor positive, and if the rheumatoid factor exceeds the upper limit of normal, it is called high (positive) rheumatoid factor. Repeated measurement of high rheumatoid factor titers often indicates a high probability of rheumatoid arthritis and that the patient's condition is in the active stage. Studies have found that more than 80% of patients with rheumatoid arthritis have a positive rheumatoid factor response. Therefore, rheumatoid factor positivity is one of the most important serological markers for diagnosing rheumatoid arthritis, but it is not the only marker. Normally, 1% to 5% of humans may be positive for rheumatoid factor. As age increases, the rate of rheumatoid factor positivity in the elderly may increase. Rheumatoid factor can also be found in many other conditions, including autoimmune, infectious, and non-infectious diseases. Autoimmune diseases include Sjögren's syndrome, systemic lupus erythematosus, progressive systemic sclerosis, juvenile rheumatoid arthritis, etc.; infectious diseases include bacterial endocarditis, tuberculosis, leprosy, infectious hepatitis, and schistosomiasis Diseases, etc.; non-infectious diseases including diffuse interstitial pulmonary fibrosis, polyarteritis, sarcoidosis, etc. Sustained elevation of rheumatoid factor often indicates disease activity of rheumatoid arthritis, with high incidence and severity of bone involvement. Studies have shown that the higher the titer of rheumatoid factor, the higher the diagnostic specificity for rheumatoid arthritis. It is generally believed that the level of IgM rheumatoid factor is not closely related to the activity of rheumatoid arthritis; the IgG rheumatoid factor is closely related to synovitis, vasculitis and extra-articular symptoms in patients with rheumatoid arthritis; the IgA rheumatoid factor is seen in rheumatoid arthritis, scleroderma etc. Rheumatoid factor is an important factor in differentiating ankylosing spondylitis from rheumatoid arthritis. Ankylosing spondylitis is a seronegative spondyloarthropathy, and seronegative means negative rheumatoid factor, and its positive rate is comparable to that of the general normal population. A small number of patients with rheumatoid arthritis are negative for rheumatoid factor, which needs to be carefully identified based on clinical symptoms, signs and other indicators.
Rheumatoid Factor Immunoglobulins
Autoimmune Rheumatoid Antibodies
Anti-IgG Autoantibodies
Rheumatoid Immune Factors
Rheumatoid Serum Factors
IgM Rheumatoid Factors
References
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