title: Fibril protein fragmentation pattern in systemic AL-amyloidosis.
abstract: Immunoglobulin light chain (AL)-amyloidosis was one of the first types of amyloidosis discovered and still little is known about its pathogenic mechanisms. One major obstacle is the very heterogeneous condition; in fact, every patient could be considered to have their own disease since symptoms and outcome vary enormously. The reason for this is not known but intrinsic factors of the immunoglobulin light chain (LC) and the fact that every LC is unique seem to be important. Post-translational modifications such as glycosylation and proteolysis are most certainly involved. By using western blotting, we studied in detail the proteolytic pattern in six patients with AL-amyloidosis of kappa type with the aid of three peptide antisera against two domains in the constant segment and one conserved domain in framework 3 of the variable region. Materials from one to five organs were analysed. The result clearly demonstrates that the fragmentation pattern was similar in amyloid of different organs in one patient but differed greatly between patients. Full-length, N-, and C-terminal fragments were detected with the three antisera. The results strongly support the hypothesis that proteolytic cleavage occurs after fibril formation.
authors.affiliation: Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Stina
authors.initials: S
authors.lastname: Enqvist
authors.forename: Knut
authors.initials: K
authors.lastname: Sletten
authors.forename: Per
authors.initials: P
authors.lastname: Westermark
mesh_terms: D000368:Aged; D000682:Amyloid / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D004386:Duodenum / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007127:Immunoglobulin Constant Regions / Q000378:metabolism; D007147:Immunoglobulin Light Chains / Q000378:metabolism*; D007135:Immunoglobulin Variable Region / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D013154:Spleen / Q000378:metabolism
chemical_list: D000682:Amyloid; D007106:Immune Sera; D007127:Immunoglobulin Constant Regions; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D010446:Peptide Fragments