Rheumatoid factors: where are we now?

Rheumatoid factors (RFs) are autoantibodies against IgG. They are probably the most studied antibody since their discovery by Waaler in 1937. In this editorial we aim to briefly examine the proposed roles of RFs, how they may contribute to disease pathogenicity, and, in so doing, mention the application of novel peptide technology, crystallography and molecular modelling to rheumatoid factor study. RFs are not exclusive to rheumatoid arthritis (RA). They are found in a number of other autoimmune diseases, such as systemic lupus erythematous and Sjogren’s syndrome, infectious diseases such a mycobacterium tuberculosis, and Lyme disease and in healthy people.1 RFs seem to have a beneficial role to the normal functioning of the immune system. They may do this in a number of ways: (1) Clearance of immune complexes. IgM and IgG RFs may bind to an antibody-antigen complex and facilitate clearance by binding to the Fc receptors on phagocytes.2 In particular, this may facilitate clearance of IgG2 and IgG4 immune complexes as these subclasses do not readily activate complement. (2) Antigen processing by B cells. B cells can act as antigen presenting cells as they can use their surface immunoglobulin to capture antigen. Membrane bound RFs can therefore capture immune complexes containing IgG that can then be internalised, which may lead to the presentation of a relevant epitope to a T cell as part of an immune response.2 …