Human rheumatoid factors bear the internal image of the Fc binding region of staphylococcal protein A.

The binding specificity of rheumatoid factors (RFs) to human Fc resembles that of some microbial Fc-binding proteins, suggesting conformational similarities in their Fc-binding regions. Using polyclonal chicken antibodies against SPA, we have detected a crossreactive determinant shared by human RFs from different individuals, but not by non-RF IgM and IgG. Chicken anti-SPA was shown to bind to 18 of 19 IgM RFs and 2 of 2 IgG RFs isolated from different individuals. This binding was inhibitable with SPA, fragment D of SPA, human IgG, and Fc fragment of IgG. The binding site for RF was located on the Fab' fragment of chicken anti-SPA. The antigenic mimicry of RFs by a protein of microbial origin suggests that the immune response to infectious agents could induce or modulate RF production through an internal image autoantiidiotype mechanism.