Experimental arthritis of rabbits caused by intra-articular injection of autologous Fab2 produced by digestion of IgG with cathepsin D. II. Microscopical and immunohistochemical findings in long-term experiments.

Over 20 successive intra-articular injections of autologous or homologous cathepsin D-Fab2 produce chronic destructive arthritis marked by dense round-cell infiltration, epitheloid hyperplasia of the lining layer, lymph nodules and a few germinal centres. 75% of the animals become Rf-positive and develop high titers of homoreactants to cathepsin D-Fab. Both these antibodies are synthesized in the synovial membrane and phagocytosed. Careful study of control animals makes it possible to exclude the possibility that the effects observed are due to the repeated joint traumata, to endo- or exotoxin-like substances, to chromatographed lysosomal material or to traces of cathepsin D. Autologous and homologous Fab2 have largely identical effects, while those of homologous or autologous IgG are much less marked. These comparisons suggest that the cathepsin D site of IgG acts as a strong antigen when exposed in the joint. The synovitis thereby induced has a pronounced tendency to spread to the left knee joint which was injected with physiological saline.