Hemodialysis: demonstration of truncated beta 2-microglobulin in AB-amyloid in situ.
Amyloid deposits of patients on long-term hemodialysis consist of a considerable proportion of beta 2-microglobulin (beta 2m) fragments, as demonstrated by N-terminal amino acid sequence analysis of isolated amyloid fibril proteins. Since this finding may have pathogenetic relevance, we have produced fragment-specific antibodies directed against a synthetic peptide of beta 2m (P132) commencing at position 20. Absorption of this antiserum on insolubilized beta 2m and subsequent isolation of the anti-P132 antibody from the insolubilized P132 peptide yielded a cleavage site-specific antibody which reacted only with P132, but not with a control fragment of beta 2m and only marginally with a beta 2m preparation in micro-ELISA. When applied onto tissue sections from various organs with AB-amyloid using an immunoperoxidase method, the fragment-specific anti-P132 antibody reacted immunohistochemically predominantly with renal AB-amyloid stones, but not with all amyloid from large joints and bone marrow amyloid-tumors, in contrast to an anti-AB or beta 2m-antibodies, which intensely stained all deposits. Thus, the presence of fragmented beta 2m-molecules have been demonstrated in amyloid in tissue sections. These data are in accordance with the results of chemical studies.
Linke
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RP
Max-Planck-Institut für Biochemie, Martinsried, München, Germany.
Kerling
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Rail
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D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000682:Amyloid / Q000032:analysis* / Q000145:classification; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D006435:Renal Dialysis; D001613:beta 2-Microglobulin / Q000032:analysis* / Q000737:chemistry / Q000276:immunology
D000682:Amyloid; D007106:Immune Sera; D010446:Peptide Fragments; D001613:beta 2-Microglobulin