title: High titers of autoantibodies to tissue factor pathway inhibitor are associated with the antiphospholipid syndrome.
abstract: 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.
authors.affiliation: Division of Haematology, Thrombosis and Haemostasis, Favaloro University, Favaloro Foundation, Buenos Aires, Argentina. forastiero@favaloro.edu.ar
authors.forename: R R
authors.initials: RR
authors.lastname: Forastiero
authors.forename: M E
authors.initials: ME
authors.lastname: Martinuzzo
authors.forename: G J
authors.initials: GJ
authors.lastname: Broze
mesh_terms: 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
chemical_list: 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