Amyloid beta 2-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 2m) 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 2m-positive amyloid deposits in these patients. Western blotting using the antibody demonstrated that beta 2m extracted from the synovium amyloid of hemodialysis patients was modified with imidazolone. Further, beta 2m isolated from the blood ultrafiltrate of hemodialyzed patients was also modified with imidazolone. In vitro incubation of beta 2m with 3-DG produced imidazolone-modified beta 2m. In conclusion, amyloid tissue beta2m is modified with imidazolone in patients with DRA. 3-DG accumulating in uremic serum may be involved in the modification of beta 2m with imidazolone.
Niwa
T
T
Nagoya University Branch Hospital, Japan.
Katsuzaki
T
T
Miyazaki
S
S
Momoi
T
T
Akiba
T
T
Miyazaki
T
T
Nokura
K
K
Hayase
F
F
Tatemichi
N
N
Takei
Y
Y
D000368:Aged; D000686:Amyloidosis / Q000209:etiology / Q000378:metabolism*; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D015153:Blotting, Western; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007093:Imidazoles / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects*; D001613:beta 2-Microglobulin / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D017127:Glycation End Products, Advanced; D007093:Imidazoles; D001613:beta 2-Microglobulin; C060458:3-deoxyglucose; D003847:Deoxyglucose