Autoantibodies to receptor induced neoepitopes of fibrinolytic proteins in rheumatic and vascular diseases.
OBJECTIVE
Abnormal plasminogen activation has been implicated in vascular and rheumatic diseases. The development of an autoimmune response to neoepitopes of plasminogen and its activator (tissue-type plasminogen activator, t-PA) was explored in sera from patients with rheumatoid arthritis (RA, n = 30), Behcet's disease (n = 20), primary antiphospholipid syndrome (APS, n = 23), and idiopathic arterial (n = 33) or venous thrombosis (n = 16).


METHODS
Sera diluted 1/50 were incubated with either plasminogen or t-PA bound to their natural receptors (immobilized fibrin or monocytic cells), and bound immunoglobulins were detected using a sheep peroxidase labeled anti-human Fab IgG. Controls included plates coated with fibrin or cells alone or plasminogen passively adsorbed to the plastic. Sera were considered positive when the absorbance at 405/490 nm was above the mean + 2 SD of normal sera.


RESULTS
Reactivity of sera against plasminogen bound to cells (28%) or to fibrin (22%) was a predominant feature in patients with RA compared with other patient groups and controls. However, some patients with primary APS had reactivity against cell and fibrin bound plasminogen (9 and 13%, respectively). Autoantibodies against fibrin bound t-PA were detected in only 8% of patients with arterial or venous thrombosis.


CONCLUSIONS
Conformational changes induced by molecular assembly of plasminogen on cell or fibrin surfaces result in the expression of neoepitopes recognized by autoantibodies. These autoantibodies could be markers of the proteolytic events associated with plasminogen activation in autoimmune diseases.
Dominguez
M
M
INSERM U143, Centre Hospitalo-Universitaire de Bicêtre, Paris, France.
Cacoub
P
P
Garcia de la Torre
I
I
Piette
T J
TJ
Salazar-Paramo
M
M
Godeau
P
P
Angleés-Cano
E
E
D000328:Adult; D000936:Antigen-Antibody Complex / Q000097:blood; D000941:Antigens / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D001666:Binding Sites, Antibody / Q000502:physiology; D002460:Cell Line / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000097:blood* / Q000276:immunology; D005337:Fibrin / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D010958:Plasminogen / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D012216:Rheumatic Diseases / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000276:immunology*; D014652:Vascular Diseases / Q000097:blood / Q000276:immunology* / Q000503:physiopathology
D000936:Antigen-Antibody Complex; D000941:Antigens; D001323:Autoantibodies; D000939:Epitopes; D011956:Receptors, Cell Surface; D005337:Fibrin; D010958:Plasminogen; D010959:Tissue Plasminogen Activator