Identification of polyclonal and monoclonal antibodies against tissue plasminogen activator in the antiphospholipid syndrome.
OBJECTIVE
To test the hypotheses that some plasmin-reactive anticardiolipin antibodies (aCL) may bind to tissue plasminogen activator (tPA) and that some of the tPA-reactive aCL may inhibit tPA activity.


METHODS
We studied the reactivity of 8 patient-derived monoclonal aCL with tPA and examined the presence of IgG anti-tPA antibodies in patients with the antiphospholipid syndrome (APS). The effects of the reactive monoclonal aCL on the activity of tPA were also examined.


RESULTS
Six patient-derived plasmin-reactive monoclonal aCL bound to tPA. Analysis of plasma samples revealed that 10 of 80 APS patients (12.5%) and 1 of 81 systemic lupus erythematosus patients (1.2%) had antibodies against fibrin-associated tPA, based on a cutoff value equal to the mean + 2SD of the level in 28 normal subjects. Of the 6 tPA-reactive monoclonal aCL, 2 of them (CL1 and CL15) inhibited tPA activity.


CONCLUSIONS
Some of the plasmin-reactive aCL in APS patients may bind to tPA. Of the tPA-reactive aCL, some (such as CL1 and CL15) may inhibit tPA activity and, thus, may be prothrombotic in the host.
Lu
Cai-Sheng
CS
University of California, Los Angeles, CA 90095, USA.
Horizon
Arash A
AA
Hwang
Kwan-Ki
KK
FitzGerald
John
J
Lin
Wei-Shiang
WS
Hahn
Bevra H
BH
Wallace
Daniel J
DJ
Metzger
Allan L
AL
Weisman
Michael H
MH
Chen
Pojen P
PP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017153:Antibodies, Anticardiolipin / Q000097:blood / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D016736:Antiphospholipid Syndrome / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000276:immunology; D010959:Tissue Plasminogen Activator / Q000276:immunology* / Q000378:metabolism
D017153:Antibodies, Anticardiolipin; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator