Degradation of a chromogenic substrate by alpha 2-macroglobulin from plasma of patients with rheumatoid arthritis.

We have shown previously that serum from patients with rheumatoid arthritis (RA) contains a polyclonal B cell activator that is associated with alpha 2-macroglobulin (alpha 2M). Some biologic effects of this activator appear to be due to a trypsin-like protease attached to alpha 2M. Therefore, in the present study, we used an anti-alpha 2M antibody solid-phase assay, with Chromozym-Try as a substrate, to determine the level of alpha 2M-protease complexes in plasma alpha 2M. We found higher levels of these complexes in RA patients than in 2 control groups. Since alpha 2M-protease complexes have been shown to induce RA-like inflammation in experimental animals and to be produced by lymphoid cells, we speculate that they may be involved in the pathogenesis of RA. However, the role of the other cells or enzyme systems in the formation of these complexes has not yet been ruled out. Results of these investigations could lead to another link between activation of the immune system and joint inflammation.