Studies into the occurrence of soluble antigen-antibody complexes in disease. 3. Rheumatoid arthritis and other human diseases.

We have found that a histamine-releasing agent, designated the rheumatoid biologically active factor (RBAF), was commonly detected in the Sephadex excluded fraction of serum and of synovial fluid obtained from patients with rheumatoid arthritis. A similar agent was also found in anaphylactoid purpura and in systemic lupus erythematosus, but not in patients with a variety of other diseases or in healthy persons. The RBAF closely resembled a soluble antigen–antibody complex, since it sedimented as a high molecular weight material and yet was specifically precipitated by goat anti-human γG-globulin. Also, the RBAF was insoluble at 50% saturation with ammonium sulphate, was stable to reduction and alkylation, underwent partial dissociation following gel filtration on Sephadex G-200 at pH 3·0, and did not stimulate the guinea-pig ileum. Moreover, the histamine-releasing activity of the RBAF was completely inhibited by human and rabbit γ-globulin. These features enabled the RBAF to be distinguished from human aggregated γ-globulin, from antibody to γ-globulin, and from anaphylatoxin, each of which also stimulated histamine release from the guinea-pig lung. The RBAF was shown to be different from both the the rheumatoid latex agglutinating factor and from the acid-dissociable γ-globulin aggregates present in the serum of some patients with rheumatoid arthritis.