Beta 2-microglobulin, different fragments and polymers thereof in synovial amyloid in long-term hemodialysis.

Amyloid deposits of a patient with long-term hemodialysis were immunohistochemically identified as beta 2-microglobulin (beta 2m)-derived. Amyloid proteins were isolated from fibril concentrates from the synovia by HPLC permeation chromatography. Further analysis included dot immunoassay, immunodiffusion, SDS-polyacrylamide gel electrophoresis and Western blotting. Proteins with molecular masses of 8.5, 12, 17 and 24 kDa as well as polymers of higher molecular mass were detected. Neither the 24-kDa dimer nor the higher polymers could be significantly reduced by disulfide reagents. The N-terminal amino-acid sequence analyses of the two major proteins of 12 and 24 kDa showed the same two sequences each: one commencing with position 1 and the other with position 7 of beta 2m. These results suggest that limited proteolysis and polymer formation independent from interchain disulfide bridging, both play a role in the genesis of beta 2m-derived amyloid in the synovia.