Collagen-anti-collagen complexes in rheumatoid arthritis sera

Immune complexes (IC) were detected in rheumatoid sera by means of anti-antibody (AA) neutralization tests. The sera with rheumatoid factor (RF) that did not agglutinate human Rh+ erythrocytes sensitized by incomplete Rh antibodies, Ripley, could be tested in an AA neutralization test without any further treatment. On the other hand, 'Ripley-positive' sera had to be treated with 2-mercaptoethanol or dithiothreitol in order to destroy RF. IC-containing sera were further studied for dispersion of IC by collagen. Surprisingly, roughly 50% of IC-containing sera were affected by collagen in that they lost AA-neutralizing activity completely or partially. Significantly, very similar results were obtained with collagen type I, collagen type II and denatured collagen type II. It was concluded that these sera contained IC formed by denatured collagen and its antibodies. Further experiments were devoted to the study of the effect of collagen on reactions of RF with Ripley-sensitized erythrocytes. In several sera, the addition of collagen eliminated the prozone. This was interpreted as deblocking of RF due to the dispersion of the blocking IC by an excess of collagen. In other sera, the addition of collagen seemed to remove or block RF. This blocking effect was interpreted as a neutralization of multispecific RF by collagen. An alternative explanation proposed that collagen formed IC with free anti-collagen antibodies and that these IC blocked the RF.