Anti‐fab' antibodies in rheumatoid arthritis

High levels of anti‐immunoglobulins that react with Fab′ fragments of IgG have been observed in sera of patients with rheumatoid arthritis (RA). To determine how much of these anti‐Fab′ antibodies are incorporated within immune complexes (IC), we added 125I‐Fab′ to sera and then measured the amount of labeled Fab′ that could be precipitated by adding polyethylene glycol (PEG). Sera were either maintained at neutral pH during this procedure or acidified (pH 3) to dissociate IC. Acidification permitted the 125I‐Fab′ an equal chance to compete with other endogenous antigens for anti‐Fab′ antibodies, once excess hydrogen ion was removed. Quantities of anti‐Fab′ in sera of 20 seropositive RA patients were greater than in sera of 43 age‐and sex‐matched healthy controls, as measured by this assay and by a solid phase radioimmunoassay. However, significantly less anti‐Fab′ antibody was incorporated in ICs in the RA patients' sera. Supernatants from cultured peripheral blood lymphocytes of RA patients also contained relatively more “free” and less “hidden” anti‐Fab′ than culture supernatants from controls. Thus there appear to be qualitative as well as quantitative differences in the anti‐Fab′ antibodies synthesized by RA patients. This may reflect different proportions of IgM and IgG anti‐Fab′ in their sera, differences in the average avidity of these antibodies, or differences in the reciprocal relationships within the idiotypic network that result in release of antibodies by certain antibody‐producing cells, but not by clones that produce complementary idiotypes.