Amyloid β2-microglobulin is modified with imidazolone, a novel advanced glycation end product, in dialysis-related amyloidosis

We have recently demonstrated by immunohistochemistry that amyloid beta(2)-microglobulin (beta(2)m) is modified with advanced glycation end products (AGEs) in dialysis-related amyloidosis (DRA). To further investigate the role of the Maillard reaction in the pathogenesis of DRA, we produced a monoclonal antibody to imidazolone, a novel AGE, and a reaction product of arginine and 3-deoxyglucosone (3-DG) which was accumulated in uremic serum. Then we determined the localization of imidazolone in the amyloid tissues by immunohistochemistry using the antibody. The connective tissues in carpal tunnel and ligamentum flavum were obtained from six patients with carpal tunnel syndrome and two patients with destructive spondyloarthropathy. Imidazolone was localized to all the beta(2)m-positive amyloid deposits in these patients. Western blotting using the antibody demonstrated that beta(2)m extracted from the synovium amyloid of hemodialysis patients was modified with imidazolone. Further, beta(2)m isolated from the blood ultrafiltrate of hemodialyzed patients was also modified with imidazolone. In vitro incubation of beta(2)m with 3-DG produced imidazolone-modified beta(2)m. In conclusion, amyloid tissue beta(2)m is modified with imidazolone in patients with DRA 3-DG accumulating in uremic serum may be involved in thr modification of beta(2)m with imidazolone.