High titers of autoantibodies to tissue factor pathway inhibitor are associated with the antiphospholipid syndrome.
As the activity of the tissue factor pathway inhibitor (TFPI) may be impaired in patients with antiphospholipid antibodies (aPL), 162 aPL patients were evaluated for autoantibodies to recombinant TFPI (anti-TFPI) using an optimized ELISA. Anti-TFPI (>18 U mL(-1) for IgG and/or > 15 U mL-1 for IgM) were detected in 54 patients with aPL (33.3%) and in three out of 79 normal controls (3.8%, P < 0.0001). Among aPL patients, the prevalence of positive anti-TFPI was 38.3 and 28.4% in those with or without diagnosis of definite antiphospholipid syndrome (APS). Patients with definite APS had a significantly greater frequency of high titer (>50 U mL(-1)) anti-TFPI than aPL patients from the no definite APS group (18.5% vs. 6.2%, OR 3.7, P= 0.017). Most aPL recognized full-length TFPI, but not a truncated form of TFPI lacking the C-terminus of the molecule. Isolated IgGs from subjects with anti-TFPI impaired the dose-dependent inhibitory effect of TFPI on factor Xa activity in the presence, but not in the absence of phospholipid vesicles. Thus, aPL with high titer anti-TFPI limit TFPI action and are associated with the APS.
Forastiero
R R
RR
Division of Haematology, Thrombosis and Haemostasis, Favaloro University, Favaloro Foundation, Buenos Aires, Argentina. forastiero@favaloro.edu.ar
Martinuzzo
M E
ME
Broze
G J
GJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008074:Lipoproteins / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000494:pharmacology; D011994:Recombinant Proteins / Q000276:immunology
D001323:Autoantibodies; D065427:Factor Xa Inhibitors; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008074:Lipoproteins; D010743:Phospholipids; D011994:Recombinant Proteins; C051928:lipoprotein-associated coagulation inhibitor; D015951:Factor Xa