Experimental arthritis of rabbits caused by intra-articular injection of autologous Fab2 produced by digestion of IgG with cathepsin D.

Intra-articularly injected autologous Fab2 produced from IgG by homologous cathepsin D induces in animals not given prior immunization acute synovitis after 1 and 3 injections, acute synovitis after 6 injections, and chronic synovitis after 12 injections. Histologically, the chronic synovitis is similar to synovitis in rheumatoid arthritis (RA). In the joint, cathepsin D Fab2 appears to act as a fairly strong antigen. Evidence for this is provided by the infiltration of large numbers of polymorphonuclear leucocytes, the marked phagocytic activity of the exudate leucocytes and tissue phagocytes, and the stimulation of the synthesis of specific antibodies (homoreactants) in the synovial plasma cells. The immediate action of injected Fab2 suggests that it forms biologically active immune complexes with homoreactants already present. These complexes are phagocytosed, the homoreactants being demonstrable immunohistochemically in inclusions of the exudate and tissue phagocytes. In addition, the local synthesis of antigammaglobulins of rheumatoid factor type is also induced. These react with heat-aggregated homologous as well as human IgG and are likewise found in inclusions in the exudate and tissue phagocytes. In the serum of the animals the titre of rheumatoid factor-like antigammaglobulins increases to an extent depending on the number of injections given. These histochemical and serological findings show striking parallels with the findings in human RA.