Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammatory proliferation of synovial membranes and progressive irreversible destruction of articular cartilage and bone. If left untreated, irreversible joint destruction or deformity can occur within 2 years. Early diagnosis and timely intervention are important to control the progression of the disease and reduce joint erosion and destruction. In recent years, the number of patients coming to the hospital for rheumatoid factor (RF) screening has been increasing year by year. Clinical studies have also confirmed that RF is a more specific indicator in the diagnosis of RA. Persistent high titers of RF in the serum often indicate disease activity in RA and a high incidence of bone erosion, and if the titers are very high, they can often be accompanied by systemic complications such as subcutaneous nodules or vasculitis, indicating a poor prognosis, so in 1958 and 1987 the American College of Rheumatology (ACR) included it in the RA classification criteria. In this criterion, clinical manifestations (symmetrical swelling of small joints, morning joint stiffness, joint pain, etc.) and X-ray indications (showing osteoporosis, cystic changes and bone erosion and joint space changes, etc.) are also important diagnostic bases. However, many people who develop joint pain are found to have a positive RF test, does this mean that they have RA? In the current serological criteria for the diagnosis of RA, RF is an autoantibody against the Fc fragment of the IgG molecule, which can be classified as IgM, IgG and IgA types according to the type of immunoglobulin. Current studies show that RF is seen in 70-80% of RA patients and is a common autoantibody in the sera of RA patients, mainly IgM type antibodies, which means that 20-30% of RA patients are still negative for RF. However, even if RF is positive, it is not necessarily RA, because RF is not only found in RA patients, but also in other autoimmune diseases of connective tissue such as systemic lupus erythematosus, dry syndrome, scleroderma, ankylosing spondylitis, gouty arthritis, reactive arthritis, psoriatic arthritis and progressive systemic sclerosis, and some non-connective tissue diseases such as infections (polyarteritis nodosa, chronic hepatitis, tuberculosis, and bronchitis, chronic systemic sclerosis, etc.). It is also elevated in patients with non-connective tissue diseases such as infections (polyarteritis nodosa, chronic hepatitis, tuberculosis, bronchitis, chronic bronchitis), liver cirrhosis, tumors, and in a few normal individuals, especially in the elderly. RF can also be detected occasionally in patients with different causes of hyperglobulinemia, leprosy, trypanosomiasis, viral infections, myocardial infarction, subacute bacterial endocarditis, paroxysmal nocturnal hemoglobinuria, allogeneic kidney transplantation, infectious mononucleosis, multiple blood transfusions, multiple prophylactic injections, leukemia, etc. Even children of RA patients, some of whom do not have RA, can also be found positive for RF. manifestations. Therefore, RF is not strictly specific for the diagnosis of RA. Moreover, generally, we cannot only look at RF (+), but mainly at the titer, which is meaningful only when it is above 1:32. An elevated RF titer in the serum often indicates that RA patients are in the active phase of the disease, and the higher the titer, the higher the specificity of RF for the diagnosis of RA, which indicates that the heavier the disease activity, the faster the progress, the less remission, the poorer the prognosis, and the combination of extra-articular manifestations. When the disease is controlled or in remission, RF decreases. Then why RF can appear in so many types of disease, and even some normal people also showed RF positive? Therefore, RF is commonly found in human body and has certain physiological roles, such as: ① can regulate the immune response of the body; ② activate complement to speed up the removal of microbial infections; ③ remove immune complexes to protect the body from damage by circulating complexes. RF is said to be positive only when the amount of RF exceeds a certain titer. It should be noted that RF produced in normal individuals has a different cellular basis and significance than that produced by RA, with synthetic naturally occurring RF being biologically important for species survival, while pathological RF in RA patients has a clear pathogenic effect. Then, what is the reason for negative serum RF in RA patients? RA patients with lymph nodes, lymph nodules, bone marrow, peripheral blood, and synovial membranes are capable of synthesizing RF, with synovial membranes and synovial fluid being the main sites of RF synthesis. Therefore, RF negative only means that no IgM.RF can be detected, and it does not mean that IgG.RF and IgA.RF are also negative. Therefore, some patients with negative RF but high clinical suspicion of RA should be further tested for IgG.RF and IgA.RF, which is called occult RF, and it has a higher rate of positivity in patients with juvenile type RA. RF is difficult to detect in normal individuals as well as in non-RA disease, and IgA.RF has a strong correlation with the severity of joint inflammation as well as bone destruction. What is the association with the presence of positive RF in normal subjects? Some data reported that the onset of RA closely related to RF may be related to age, occupation, geography, climate, exposure to cold and humidity, overexertion, lifestyle, diet and living and other causative factors, and the RF positive rate is higher in women than in men. The findings also showed that the RF positivity rate was higher in people who habitually consumed high-fat foods than in those who habitually consumed low-fat foods, while the incidence of rheumatoid arthritis was reduced in people who regularly consumed unsaturated fatty acids such as fish oil or olive oil. Because the oxidation process of fat in the body can produce too much ketone bodies, and excessive ketone body production, which has a strong irritating effect on the joints, will aggravate the condition of rheumatoid arthritis. Therefore, rationalization of diet has a role in reducing the positive rate of RF and can prevent the occurrence of autoimmune diseases associated with RF, especially rheumatoid arthritis. In recent years, with the progress of autoimmune disease research, a variety of autoantibodies with high specificity for RA have been discovered for the diagnosis of RA, especially for RF-negative or early RA with more diagnostic or predictive value. For example, anti-perinuclear factor (APE), anti-keratin antibody, anti-cyclic citrullinated peptide antibody (anti-CCP antibody), anti-RA33 antibody, anti-Sa antibody, etc. The sensitivity and specificity of combined testing of multiple indicators is higher. Therefore, there should be a correct understanding of RF positivity, which should never be regarded as equal to RA, and arthralgia + RF positivity does not necessarily mean RA. RF positivity is not only seen in RA, but also in normal people or certain diseases, not to mention the presence of occult RF and IgG-RF and IgA.RF, etc. Clinical diagnosis of RA, especially early RA, combined with the detection of other antibodies, combined with clinical manifestations, other laboratory tests and imaging findings to analyze, in order to make a correct diagnosis of the disease and improve the diagnosis rate of RA.