Identification of pentosidine as a native structure for advanced glycation end products in beta(2)-microglobulin-containing amyloid fibrils in patients with dialysis-related amyloidosis

beta(2)-Microglobulin (beta(2)m) is a major constituent of amyloid fibrils in patients with dialysis-related amyloidosis (DRA), Recently, we found that the pigmented and fluorescent adducts formed nonenzymatically between sugar and protein, known as advanced glycation end products (AGEs), were present in beta(2)m-containing amyloid fibrils, suggesting the possible involvement of AGE-modified beta(2)m in bone and joint destruction in DRA, As an extension of our search for the native structure of AGEs in beta(2)m of patients with DRA, the present study focused on pentosidine, a fluorescent cross-linked glycoxidation product. Determination by both HPLC assay and competitive ELISA demonstrated a significant amount of pentosidine in amyloid-fibril beta(2)m from longterm hemodialysis patients with DRA, and the acidic isoform of beta(2)m in the serum and urine of hemodialysis patients. A further immunohistochemical study revealed the positive immunostaining for pentosidine and immunoreactive AGEs and beta(2)m in macrophage-infiltrated amyloid deposits of long-term hemodialysis patients,vith DRA. These findings implicate a potential link of glycoxidation products in long-lived beta(2)m-containing amyloid fibrils to the pathogenesis of DRA.