Leucocyte migration inhibition with IgG-IgG complexes and rabbit IgG fragments in patients with rheumatoid arthritis.

The interaction of leucocytes from patients with rheumatoid arthritis and from healthy control subjects with IgG–IgG complexes and IgG fragments has been assessed using leucocyte migration inhibition. IgG–IgG complexes were prepared and fractionated by gel filtration on Sepharose CL-6B. Significant inhibition of rheumatoid leucocyte migration was observed in the presence of IgG–IgG complexes at a protein concentration of 5 μg/ml. This concentration of complexes had no effect on control cells. The rheumatoid leucocytes showed a twenty- to forty-fold increase in reactivity to complexed IgG as compared with the native protein. The inhibitory effect was mediated through the Fc region of the IgG molecule but was independent of complement. Native rabbit IgG inhibited both rheumatoid and control leucocyte migration. Rabbit F(ab') was inactive however, whereas the Facb fragment (from plasmin digestion) caused specific inhibition of rheumatoid cells. Little reactivity was seen with Fab or with Fc fragments. The present study demonstrates that rheumatoid leucocytes react abnormally to IgG and provides the first direct evidence that this reactivity is directed largely against determinants in the C2 region of the molecule. The response of rheumatoid leucocytes to this region is significantly increased if the IgG is complexed to antigen or subjected to limited proteolysis. Both these processes are associated with inflammatory reactions and may be responsible for producing the altered IgG structure which induces the antiglobulin response in rheumatoid arthritis.