Anti-t-PA antibodies in acute myocardial infarction after thrombolysis with rt-PA.
BACKGROUND
Thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) is successfully used in acute myocardial infarction with ST elevation (STEMI). Reocclusions follow rt-PA treatment in up to 30% of patients within one year. The infusion of rt-PA may induce the production of anti-t-PA antibodies which could interfere with the function of the native t-PA molecule.


METHODS
In order to detect and characterise anti-t-PA antibodies, plasma samples were collected from 30 STEMI patients (20 treated and 10 not treated with rt-PA) at baseline before rt-PA infusion and then 15, 30, 90 and 180 days after STEMI and from 40 healthy subjects at baseline only. Immunoenzymatic, chromatographic and chromogenic methods were employed.


RESULTS
An increase of anti-t-PA antibodies was observed 15 days (IgM, p=0.0001) and 30 days (IgG, p=0.0001) after rt-PA infusion. Six patients had large increases of anti-t-PA IgG which bound the catalytic domain of t-PA (two cases) or kringle 2 domain (four cases), were of IgG1 or IgG3 subclasses and interacted with the t-PA molecule in fluid phase.


CONCLUSIONS
The infusion of rt-PA may induce the production of specific antibodies that bind active sites of t-PA, thus potentially reducing its in vivo function.
Cugno
Massimo
M
Department of Internal Medicine, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Via Pace 9, 20122, Milan, Italy. massimo.cugno@unimi.it
Castelli
Roberto
R
Bisiani
Giuliana
G
Griffini
Samantha
S
Meroni
Pier Luigi
PL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D004562:Electrocardiography; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000276:immunology / Q000627:therapeutic use*
D000906:Antibodies; D001323:Autoantibodies; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator