Antibodies to prothrombin crossreact with plasminogen in patients developing myocardial infarction.
In a prospective study on healthy middle-aged men, high level of antibodies to prothrombin implied a risk of myocardial infarction. The possible mechanism(s) of these antibodies in coronary thrombosis are not known. Because prothrombin belongs to the kringle proteins and shares structural homology with a fibrinolytic kringle protein plasminogen, we studied whether antibodies to prothrombin crossreact with plasminogen. Sera from 17 healthy middle-aged men who later developed myocardial infarction were studied. Binding of antibodies to immobilized prothrombin (EIA) was inhibited by using soluble prothrombin, plasminogen and synthetic peptides of 20 amino acids from plasminogen kringle 5 (P304, P305) and from prothrombin kringle 2 (P302) as inhibitors. The peptides contained the conserved pentapeptide CRNPD of the kringle proteins. Soluble prothrombin inhibited up to 50% the binding of antibodies to immobilized prothrombin in all sera. Plasminogen inhibited binding in 9/17 (53%) sera (a decrease of at least 20%). P305 inhibited binding to prothrombin in 8/17 (47%), P304 in 4/17 (23%) and P302 in 6/17 (35%) sera. In structural analysis, presentation of the pentapeptide was conformationally different between the peptides. We conclude that crossreactive antibodies binding to prothrombin and plasminogen occur in sera of patients later developing myocardial infarction. The crossreactive epitope seems to be conformational and include the conserved pentapeptide of the kringle proteins. These antibodies may interfere with the fibrinolytic function of plasminogen and contribute to the development of myocardial infarction.
Puurunen
M
M
Department of Biochemistry, National Public Health Institute, Helsinki, Finland.
Mänttäri
M
M
Manninen
V
V
Palosuo
T
T
Vaarala
O
O
D000906:Antibodies / Q000276:immunology*; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000276:immunology*; D010958:Plasminogen / Q000276:immunology*; D011446:Prospective Studies; D011516:Prothrombin / Q000276:immunology*
D000906:Antibodies; D007074:Immunoglobulin G; D011516:Prothrombin; D010958:Plasminogen