MACROMOLECULES THAT ARE COLOCALIZED WITH DEPOSITS OF BETA-2-MICROGLOBULIN IN HEMODIALYSIS-ASSOCIATED AMYLOIDOSIS

BACKGROUND: Common elements in many different types of amyloid may hav e important roles in amyloidogenesis. The proteinaceous tissue deposit s have a common appearance in polarized light and other similar featur es. The present investigation describes for the first time the relatio n between beta2-microglobulin (beta2-M)-type amyloidosis and colocaliz ed materials, as demonstrated using specific antibodies and hyaluronan -binding protein. EXPERIMENTAL DESIGN: Amyloid-rich carpal tunnel syno vium was obtained surgically from 28 patients who were being treated b y maintenance hemodialysis. Serial sections were examined using a hyal uronan (hyaluronic acid)-binding protein and antibodies against hepara n sulfate-glycosaminoglycan, chondroitin sulfate-proteoglycan, dermata n sulfate-proteoglycan, alpha1-antichymotrypsin, alpha1-antitrypsin, i nter-alpha-trypsin inhibitor, haptoglobin, and ubiquitin. RESULTS: Acc umulation of hyaluronan was of three types, namely, localization aroun d beta2-M deposits, colocalization with deposition of beta2-M itself a nd localization at a small distance from beta2-M deposits. Immunostain ing for heparan sulfate glycosaminoglycan was demonstrated at the site s Of beta2-M plaques. Chondroitin sulfate-proteoglycan did not show sp ecific patterns of immunostaining, resembling hyaluronan rather than h eparan sulfate. The other materials tested, alpha1-antichymotrypsin, a lpha1-antitrypsin, inter-alpha-trypsin, haptoglobin and ubiquitin, wer e not immunostained at sites Of beta2-M plaques. Sodium dodecyl sulfat e-polyacrylamide gel electrophoresis and immunoblotting revealed that the molecular weight of heparan sulfate-glycosaminoglycan was 16,000. CONCLUSIONS: These results suggest that HS has an important role in he modialysis-associated amyloidosis as it does in other types of amyloid osis. Moreover, accumulation of hyaluronan may be an indication of inf lammation of the carpal synovium.