Rheumatoid factor (RF) is a household name. Non-rheumatologists may diagnose rheumatoid arthritis (RA) when they see a positive RF, combined with joint pain. And the general public like to RF and “rheumatism” associated or even equated, so for this most familiar stranger – RF, we really understand him? First, the discovery of RF and the nature of the discovery of RF The first reported RF is Cecil and others, around 1931 they found that the serum of patients with RA has the role of agglutination of bacteria such as streptococcus. Then in 1940, a Norwegian physician, Dr. Waaler, discovered in his experiments the presence of a factor in the serum of RA patients that caused the agglutination of sensitized sheep red blood cells. Pick, a New York physician, named this agglutination factor RF in 1949 and popularized it in clinical practice. What exactly is RF? It is now believed that RF is an antibody produced in the body due to infectious agents (bacteria, viruses, etc.) with denatured IgG as the antigen, so it is also called anti-antibody, and can be divided into five types: IgM, IgA, IgG, IgD and IgE. Among them, IgM-RF is the most common in patients with RA, plays a major role, easy to determine, so we generally test for IgM-RF. Second, the most commonly used detection methods for RF More than 50 years ago, Waaler’s experiments pioneered the basic method of RF determination – sheep erythrocyte agglutination legal test, but the method Only negative and positive results can be obtained. The current RF assays are: latex agglutination, ELISA (enzyme linked immunosorbent assay) and immunoturbidimetric assays (transmission turbidimetry, scattering turbidimetry, latex enhanced turbidimetry). The latter two methods can be used for the quantitative determination of RF, and ELISA can be used for the determination of RF and its subtypes. The clinical significance of RF The pathogenic mechanism of RF is currently considered that microbial infections such as cytomegalovirus stimulate the production of anti-IgG antibodies, which is RF, and RF and IgG form immune complexes deposited in the synovial membrane and other tissues, activating the complement system to produce C5a and C5b-C9 MAC, which in turn forms a complex and unstoppable “immune activation loop”, gradually causing synovial membrane, joint capsule, cartilage and bone The result is a complex “immune activation loop” that gradually causes damage to the synovium, joint capsule, cartilage and even bone, resulting in joint damage or even deformation. Does RF positivity always mean RA? RF has a positive rate of 60% to 80% in patients with RA and is an important serologic criterion for the diagnosis of RA, but is generally specific, as it is also seen in other diseases and healthy individuals. For example, in elderly people aged >75 years, the positivity rate can be 5%-25%, and in family members of RA patients, the positivity rate can be 5%-22%, but they do not necessarily have RA. RF positivity can also be seen in other diseases such as autoimmune diseases (systemic lupus erythematosus, scleroderma, dry syndrome, etc.), infectious diseases (EBV infection, cytomegalovirus infection, hepatitis B infection, subacute infective endocarditis, etc.), diffuse interstitial lung fibrosis, liver disease, nodular disease, and macroglobulinemia. Non-RA “normal” individuals with high titers of RF in their serum do have a high risk of developing RA and should be followed up closely. Does a negative RF mean that you do not have RA? A negative RF test does not mean that you are not RA. There is a type of RA patient who has a negative RF test called “seronegative”. Some patients with RA have negative RF because 1. the rate of positivity varies by test method and 2. the method used to measure IgM-RF may miss IgA-RF or IgG-RF. 20% to 30% of RA patients have negative RF tests. Generally, patients with RF-negative RA have milder disease than RF-positive patients and rarely develop vasculitis, extra-articular lesions such as neuropathy, subcutaneous nodules, and overlap syndrome. In patients with negative RF and a high clinical suspicion of RA, RF in immune complexes, or occult RF, can also be measured, especially in patients with juvenile rheumatoid arthritis, where the positive rate is higher. What kind of RF is the real “Li Kui”? RF should meet the following criteria to be meaningful for the diagnosis of RA: 1. high titer; 2. two or more positive tests; 3. positive results of multiple tests; 4. reactive with both human and animal IgG molecules; 5. IgG, IgA, or IgE RF in addition to IgM RF. RF is on the way to get new skills A study showed that RF-positive patients with dry syndrome are more likely to have lung damage than RF-negative patients. RF-negative patients are more likely to have lung involvement, arthritis, parotid enlargement, hematological involvement, etc. Several studies have shown that RF positivity can indicate interstitial lung disease and become one of the predictors of lung involvement.