Antiphosphatidylserine/prothrombin antibodies in primary antiphospholipid syndrome.

Antiprothrombin (aPT) antibodies may be detected by an enzyme-linked immunosorbent assay (ELISA) using a purified antigen or a phosphatidylserine/prothrombin complex (aPS/PT). IgG/IgM antibodies directed against aPS/PT were assessed in 158 patients with primary antiphospholipid syndrome (PAPS). They were detected in 80/158 (50.6%) PAPS patients; IgG alone was positive in 12 (7.6%), IgM alone in 36 (22.8%), and both IgG and IgM isotypes in 32 (20.2%) PAPS patients. IgG and IgM aPS/PT were significantly associated with both vascular thrombosis and pregnancy morbidity. IgG aPS/PT was significantly associated with venous thrombosis (p = 0.023), whilst IgG and IgM aPS/PT were associated with arterial thrombosis (p < 0.001 and p < 0.001, respectively). Logistic regression analysis showed that IgM and IgG aPS/PT were independent risk factors for thrombosis (odds ratio (OR) 3.5 [95% confidence interval (CI) 1.6-7.9] and OR 4.1 [95% CI 1.4-11.7], respectively) and IgM aPS/PT was an independent risk factor for arterial thrombosis (OR 2.7 [95% CI 1.1-6.7]). In conclusion, these findings indicate that aPS/PT are clinically relevant in PAPS.

The clinical significance of autoantibodies directed against prothrombin in primary antiphospholipid syndrome.

BACKGROUND: To evaluate the clinical significance of IgG/IgM antibodies directed against prothrombin (PT) in a homogeneous cohort of patients with primary APS (PAPS). METHODS: IgG/IgM anti-prothrombin (aPT) antibodies were measured using a commercial ELISA kit in 158 PAPS patients and in 214 control subjects (100 healthy blood donors and 114 patients with autoimmune diseases). RESULTS: IgG/IgM aPT antibodies were significantly associated with PAPS (OR, 95% CI: 52.0, 7.0-385.5; 9.8, 1.2-80.8, respectively). They were found to have a high specificity (IgG 99.50%, IgM 99.54%) but a low sensitivity (IgG 19.60%, IgM 3.80%) for PAPS. IgG aPT antibodies were significantly higher in the PAPS patients with thrombosis (OR, 95% CI: 69.2, 9.2-519.1) as well as in those with pregnancy morbidity alone (OR, 95% CI: 20.5, 2.4-174.5). The prevalence of IgG aPT was not significantly different in the thrombotic and obstetric patients, and the presence of IgM aPT antibodies was significant only in patients with thrombosis (OR, 95% CI: 2.6, 1.6-110.8). CONCLUSIONS: The study's findings confirm that IgG/IgM aPT antibodies are significantly associated with PAPS and indicate that IgG aPT antibodies are associated with clinical subsets of the disease. For the time being, however, the lower sensitivity of IgG/IgM antibodies with respect to conventional aPL antibodies precludes their inclusion in the recommendations for the diagnosis of PAPS.

[Clinical value of antibodies to lysobisphosphatidic acid in patients with primary antiphospholipid syndrome]. / Significato clinico degli anticorpi anti acido lisobisfosfatidico nei pazienti con sindrome da antifosfolipidi primaria.

To assess the clinical value of anti-lysobisphosphatidic acid (anti-LBPA) antibodies in patients with primary antiphospholipid syndrome (APS), the sera of 140 primary APS patients were tested and compared with those of 70 control subjects affected with rheumatic systemic diseases (n. 24) or autoimmune thyroiditis (n. 46). Anti-LBPA anticardiolipin (aCL) and anti-beta2 Glycoprotein I (anti-beta2GPI) antibodies were determined using a "home made" ELISA method. Lupus anticoagulant (LA) was assessed using a series of clotting tests in accordance with the literature. IgG anti-LBPA was significantly prevalent in primary APS (p=0.000) with a sensitivity of 58.6% and a specificity of 92.9%. IgM anti-LBPA showed a significant frequency in primary APS (p=0.000) with a sensitivity of 28.6% and a specificity of 97.1%. Anti-LBPA's sensitivity and specificity for APS were lower or equal to those of aCL and anti-beta2GPI. The prevalence of anti-LBPA in the different clinical and laboratory subsets of APS was lower than those of aCL and anti-beta2GPI. It is interesting to observe that both IgG and IgM anti-LBPA were never found alone. The comparison between anti-LBPA and LA showed that the former had a higher sensitivity but a lower specificity. In conclusion, in view of our results anti-LBPA cannot at present be considered a further tool to be utilized to diagnose APS and to differentiate the different clinical and laboratory subsets of this disease.

[Confirmation of antiphospholipid antibody positivity: a year's results in a cohort of 113 patients]. / Conferma della positività nell'autoimmunità antifosfolipidica: risultati acquisiti in un anno in una coorte di 113 pazienti.

OBJECTIVE: To evaluate the confirmation rate of antiphospholipid antibodies (aPL), to analyze their behaviour at confirmation time, and to study the clinical value of their confirmation. METHODS: Blood samples from 380 subjects, enrolled in this study from June 1, 2007 to May 31, 2008, were tested for anti-cardiolipin (aCL) and anti-beta2glycoprotein (abeta2GPI) antibodies using an ELISA method and for Lupus anticoagulant (LA) using a series of clotting tests. The samples of the 113 subjects resulting positive at the first testing time were assayed again to confirm antiphospholipid positivity. RESULTS: aPL positivity was confirmed in 67 out of the 113 subjects (59.3%). Medium-high antibody levels of all, except IgM aCL, aPL/ELISA had a significantly higher confirmation rate with respect to that in subjects with low levels. The confirmation rate in the category I antibody patients (multiple positivity) was higher than that in the category II antibody subjects (single positivity). LA positivity was confirmed only when it was associated to other aPL. The cut-off of 40 GPL produced a confirmation rate equal to that resulting from a 99th percentile cut-off. Confirmation of aPL positivity made it possible for us to confirm the diagnosis of antiphospholipid syndrome (APS) in 8 out of the 113 subjects originally resulting positive (7.1%). APS clinical features were vascular thrombosis in 4 of these and pregnancy morbidity in the other 4. CONCLUSIONS: Our data emphasize aPL positivity confirmation selectivity, and medium-high antibody levels and category I antibodies (multiple positivity) had the best confirmation rates.

Influence of different IgG anticardiolipin antibody cut-off values on antiphospholipid syndrome classification.

BACKGROUND: While medium to high titers of anticardiolipin (aCL) antibodies, defined as >40 GPL units or >99th percentile, is a laboratory criteria for the 'definite' diagnosis of antiphospholipid syndrome (APS), agreement between the two cut-offs has not been validated. OBJECTIVE: To validate the current aCL laboratory criterion by verifying the effect of the two cut-offs on APS classification. PATIENTS/METHODS: Ninety aCL positive APS patients were selected on the basis of their GPL values above the 99th percentile (17.4 GPL), which was calculated by testing 100 age- and sex-matched healthy subjects. RESULTS: A significant difference in the IgG positivity (P < 0.0001) was found between the APS laboratory profiles as 20 out of the 24 (83.3%) patients with single positivity (aCL alone), six out of the 23 (26.1%) with double positivity (aCL plus lupus anticoagulant or anti-beta(2)glycoprotein I), and none out of the 43 with triple positivity (aCL plus lupus anticoagulant and anti-beta(2)glycoprotein I) had titers between the 99th percentile and 40 GPL units. Moreover, the rate of aCL values between the 99th percentile and 40 GPL units was significantly higher (P < 0.0001) in patients with pregnancy morbidity (73.7%) as compared to those with vascular thrombosis (16.9%) and those with both conditions (16.7%). CONCLUSION: The 99th percentile cut-off level seems more sensitive than the >40 GPL value for APS classification, as it includes subjects with aCL positivity alone as well as patients with pregnancy morbidity.