Cathepsin D agglutinators and neutral protease agglutinators in rheumatoid arthritis. II. Production of CDA and NPA by rheumatoid synovium and phagocytosis of CDA by synovial phagocytic cells.

Tissue culture methods demonstrated the production of agglutinators against the cathepsin D site in IgG (CDA) and a neutral protease site in IgG (NPA) by rheumatoid synovial tissue. Seven of 11 specimens from seropositive and 2 of 7 specimens from seronegative RA patients were positive for CDA, whereas 2 of 11 specimens from seropositive and 1 of 7 specimens from seronegative patients were positive for NPA. None of the 6 control specimens was positive for both types of agglutinators. Chromatography of two synovial tissue incubates showed that the CDA were of the IgG type. By the immunofluorescence technique, plasma cells containing CDA were demonstrated in rheumatoid synovial tissue and draining lymph nodes of rheumatoid joints. The staining for CDA in the synovium was different from the staining for pepsin agglutinators in adjacent sections. Phagolysosomes containing CDA were found in synovial exudate cells from rheumatoid patients as well as in phagocytosing lining cells and macrophages of the sublining layer of rheumatoid synovial tissue. These findings suggest that antibodies directed at hidden antigenic sites in IgG revealed by endogenous proteolysis take part in the immune reaction and in the inflammation of rheumatoid joints.