[Pathogenesis of amyloidosis: a role for anti-proteases?]

A new type of amyloidosis has been observed which appears in long-term survivors on haemodialysis, with beta 2-microglobulin identified as its major protein constituent. We recently identified alpha 2-macroglobulin, the major serum anti-protease, in amyloid deposits of haemodialysis patients. It has also been reported that amyloid fibrils can be redissolved in vitro by proteases. These findings, coupled with the facts that alpha 2-macroglobulin blocks the proteases and decreases macrophage production of proteases, suggest that alpha 2-macroglobulin may prevent the degradation of the amyloidogenic protein allowing amyloid deposit formation and/or persistence. In our opinion, alpha 2-macroglobulin and possibly other antiproteases as well, may play a key role in amyloidogenesis in dialysis patients.