Human Rheumatoid factor is an autoantibody found in rheumatoid arthritis. Rheumatoid factor is an antibody which is formed against the Fc portion of the IgG antibody. These two together (Rheumatoid factor and IgG) are responsible for formation of immune complexes which contribute to the process of disease and its progression. Rheumatoid arthritis can be a cryoglobulin which is an antibody that precipitates outs when the blood sample is cooled or can be type 2 which includes monoclonal antibody IgM or polyclonal antibody IgG or can be of type 3 which is the polyclonal IgM to polyclonal IgG cryoglobulin. Rheumatoid factor is predominantly found to be as IgM, but it can be an isotype of IgA, IgM, IgG, IgD or IgE immunoglobulin.

The crystal structure analysis of the complex of autoantibody and its autoantigen shows that there relatively few contact residues of the antibody which contributes to its low affinity. Rheumatoid factor is found in patients with arthritis. The presence of rheumatoid factor combined with other signs and symptoms can play a big role in diagnosis and prognosis of the disease. Rheumatoid factor in serum indicates suspected autoimmune activity which may or may not be related to rheumatoid arthritis. This includes organ or tissue rejection and can serve as a serological marker for autoimmunity. Healthy individuals usually do not produce rheumatoid factor. 30% of normal individuals may show rheumatoid factors but these have very low affinity and titer which does not carry any pathological significance. Increased levels of rheumatoid factor occurs in rheumatoid arthritis and Sjögren’s syndrome. The high levels of rheumatoid factor also indicates the chances of destructive articular disease. Rheumatoid factor is also observed in Parvovirus and Epstein-Barr virus infections. The test for rheumatoid factor was first introduced by Dr. Erik Waaler and re-described by Dr. H.M. Rose. The test for rheumatoid factor testing is referred as Waaler-Rose test.