The Structure of a Human Rheumatoid Factor Bound to IgG Fc

Rheumatoid factors (RF) are autoantibodies with reactivity towards the Fc regions of IgG molecules (1). They are found in the sera and synovia of most patients with rheumatoid arthritis (RA), and high levels of RF are associated with severe disease and poor prognosis (2,3) suggesting that they have a causative role in the pathology of this disease. The IgM or IgG RFs form immune complexes with IgG molecules in the joints, which can then activate complement and cause inflammation. However, not all RFs cause disease, and the distinction between “pathological” and “physiological” RFs is not understood (4).