Anti-prothrombin antibodies predict thrombosis in patients with systemic lupus erythematosus: a 15-year longitudinal study.
OBJECTIVE
To evaluate the role of anti-prothrombin (anti-PT) antibodies in predicting thrombosis in patients with systemic lupus erythematosus (SLE).


METHODS
An inception cohort of 101 SLE patients (12 males, 89 females; mean age 30 +/- 8 years), was considered. Clinical and laboratory evaluations were regularly performed during a 15-year follow-up (median 108 months) with a special focus on thromboembolic events. Serum samples were collected at time of diagnosis and at least once a year thereafter. IgG and IgM anti-PT, anti-cardiolipin (aCL) and anti-beta(2)glycoprotein I (beta(2)GPI) antibodies were measured by enzyme-linked immunosorbent assay (ELISA); lupus anticoagulant (LAC) was assayed by the dilute Russell's viper venom time and activated partial thromboplastin time tests. The analytical specificity of anti-PT ELISA was investigated. The timing of thrombosis occurrence was calculated using the Kaplan-Meier method.


RESULTS
In the 15-year follow-up, thrombosis occurred in 14 out of the 101 patients: venous thrombosis in nine cases and arterial thrombosis in five. IgG and/or IgM anti-PT, anti-beta(2)GPI and aCL antibodies, and LAC activity were detected in ten, nine, seven, and nine cases, with sensitivity for thrombosis of 71.4%, 64.3%, 50% and 64.3%, respectively. Thrombosis-free survival was 90% at 5 years and 85.8% at 10 and 15 years, respectively. Thrombosis was predicted by anti-PT (P = 0.001), anti-beta(2)GPI antibodies (P = 0.002) and LAC activity (P = 0.001). Moreover, the risk of thrombosis progressively increased with the number of positive antiphospholipid antibody tests. The presence of four positive antibody tests was associated with a risk of thrombosis thirtyfold higher than in their absence.


CONCLUSIONS
This longitudinal study shows that IgG anti-PT antibodies are predictors of thrombosis in SLE patients.
Bizzaro
N
N
Laboratory of Clinical Pathology, Hospital of Tolmezzo, Tolmezzo, Italy.
Ghirardello
A
A
Zampieri
S
S
Iaccarino
L
L
Tozzoli
R
R
Ruffatti
A
A
Villalta
D
D
Tonutti
E
E
Doria
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D017152:Antibodies, Antiphospholipid / Q000097:blood; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011516:Prothrombin / Q000276:immunology*; D012307:Risk Factors; D013923:Thromboembolism / Q000097:blood / Q000209:etiology / Q000276:immunology; D013927:Thrombosis / Q000097:blood / Q000209:etiology* / Q000276:immunology*
D017152:Antibodies, Antiphospholipid; D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011516:Prothrombin