β2-Microglobulin (β2m) 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 β2m-containing amyloid fibrils, suggesting the possible involvement of AGE- modified β2m in bone and joint destruction in DRA. As an extension of our search for the native structure of AGEs in β2m 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 β2m from long-term hemodialysis patients with DRA, and the acidic isoform of β2m in the serum and urine of hemodialysis patients. A further immunohistochemical study revealed the positive immunostaining for pentosidine and immunoreactive AGEs and β2m in macrophage-infiltrated amyloid deposits of long-term hemodialysis patients with DRA. These findings implicate a potential link of glycoxidation products in long-lived β2m-containing amyloid fibrils to the pathogenesis of DRA.
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Publication status||Published - 1996|
ASJC Scopus subject areas