Discriminating neoantigenic differences between fibrinogen and fibrin derivatives.
Discrimination between the physiological cleavage fragments of fibrinogen and fibrin offers an approach to differentiation between fibrinogenolytic processes and fibrinolysis after coagulation. By use of the cleavage-associated neoantigen of fibrinogen (fg-D(neo)) as a molecular marker, characteristic differences between the D regions of fibrinogen derivatives and fibrin derivatives can be demonstrated. The expression of fg-D(neo) by X, Y, D:E complex, and D-fragments of fibrinogen or fibrin is shown to be quantitative and unitary. Characteristic differences between fg-D(neo) sites present on fibrinogen cleavage fragments, as contrasted to fibrin cleavage fragments, are indicated by different competitive inhibition slopes, and appear to reflect differential binding affinity of selected anti-fg-D(neo) antibodies for the specific molecular site. There is a linear relationship between the slope of quantitative competitive inhibition and the relative molar ratio of fibrinogen and fibrin derivatives. Identical immunochemical expressions are observed in vitro and in vivo, and support the thesis that cleavage in vivo is produced by plasmin. The differential immunochemical features of fg-D(neo) expression may be the result of stable conformational and/or subtle structural differences between the D region of fibrinogen and fibrin cleavage fragments and suggest that precise changes in the D region are associated with the fibrin transition. These molecular features not only provide additional insight into the molecular immunology and structure of fibrinogen, but also appear to offer a new molecular approach to discrimination between fibrinogenolytic mechanisms as contrasted to fibrinolysis secondary to coagulation.
D000037:Abruptio Placentae / Q000097:blood; D058186:Acute Kidney Injury / Q000097:blood; D000230:Adenocarcinoma / Q000097:blood; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D001778:Blood Coagulation Disorders / Q000097:blood; D000939:Epitopes; D005260:Female; D005337:Fibrin; D005340:Fibrinogen; D005341:Fibrinolysin; D005342:Fibrinolysis; D006801:Humans; D007106:Immune Sera; D007456:Iodine Isotopes; D008297:Male; D008545:Melanoma / Q000097:blood; D008589:Meningococcal Infections / Q000097:blood; D010538:Peritonitis / Q000097:blood; D011247:Pregnancy; D011471:Prostatic Neoplasms / Q000097:blood; D011863:Radioimmunoassay; D013329:Structure-Activity Relationship
D000939:Epitopes; D007106:Immune Sera; D007456:Iodine Isotopes; D005337:Fibrin; D005340:Fibrinogen; D005341:Fibrinolysin