Prevalence and clinical correlations of antibodies against six beta2-glycoprotein-I-related peptides in the antiphospholipid syndrome.

Two-hundred ninety five patients with the antiphospholipid syndrome (APS) were studied for the presence of antibodies against six anti-beta2GPI-related peptides Abs. The prevalence of a wide spectrum of clinical and laboratory parameters of APS was evaluated in all patients, and correlated with the presence of each anti-beta2GPI peptide antibody. The rates of the various antipeptides Abs ranged from 18.0 to 63.7%. Altogether, 87.1% of the patients had antibody reactivity against at least one of the six beta2GPI-related peptides. A high degree of simultaneous reactivity against several beta2GPI-peptides was found. Positive and negative correlations were found between several antipeptides Abs and the rates of thrombosis and fetal loss. Our results point to a heterogeneous activity of antiphospholipid Abs in APS patients, directed, often concurrently, against various epitopes of the beta2GPI molecule. Evaluation of APS patients for the presence of specific antipeptides Abs may be of a value in predicting the risk for future thrombotic and obstetrical complication, as well as for specific therapeutic purposes.

Antiprothrombin antibodies are associated with pregnancy loss in patients with the antiphospholipid syndrome.

OBJECTIVE: To document the clinical association between the history of pregnancy loss in patients with the diagnosis of primary or secondary antiphospholipid syndrome (APS) and the presence of different antiprothrombin antibody subtypes [immunoglobulin G (IgG), IgM and IgA] in a cohort of patients with APS. METHODS: Records of 170 female patients with primary APS, or APS secondary to systemic lupus erythematosus (SLE) or secondary to other autoimmune diseases were studied. RESULTS: In female APS patients with IgG antiprothrombin antibodies (n = 105) significant associations to pregnancy loss (p < 0.0001), early pregnancy loss (p < 0.0001) and a negative association to thrombocytopenia (p < 0.01) could be identified. In the group of patients with IgG antiprothrombin antibodies and at least one pregnancy (n = 84) a significant association with pregnancy loss (p < 0.005) and especially with early pregnancy loss (p < 0.0001) was demonstrated. No association with other immunoglobulin subtypes of antiprothrombin antibodies could be documented. In the subgroup of patients with primary APS and at least one pregnancy in the history, pregnancy loss (p < 0.005) and early pregnancy loss (p < 0.0001) were found to be highly associated with the presence of IgG antiprothrombin antibodies. IgG antiprothrombin antibodies represent the highest independent risk factor for pregnancy loss with an odds ratio of 4.5. There was no statistically significant association with venous or arterial thrombosis in all IgG antiprothrombin antibody positive patients. CONCLUSION: The results of this study document the association of IgG antiprothrombin antibodies with pregnancy loss and in particular early pregnancy loss in a large and well-characterized cohort of patients. We would recommend routine testing for antiprothrombin antibodies in young female patients with APS.

Behavioral and cognitive deficits occur only after prolonged exposure of mice to antiphospholipid antibodies.

The antiphospholipid (Hughes) syndrome (APS) includes systemic and central nervous system (CNS) pathology associated with antibodies to a complex of phospholipids and beta2-glycoprotein I (beta2-GPI). Beta2-GPI immunized mice develop systemic manifestations of APS and we presently examined CNS manifestations in this APS model. Female BALB/c mice were immunized once with beta2-GPI in complete Freund's adjuvant (CFA) or with CFA alone (controls). A staircase test and a T-maze alternation test were performed to test behavior and cognition in independent groups of mice 6, 12 and 18 weeks following the immunization. The APS mice developed elevated levels of antibodies against negatively charged phospholipids and beta2-GPI. Neurological impairment was detected only 18 weeks after the induction of the APS and consisted of both cognitive (53 +/- 4 vs 71 +/- 3% correct choices in the T-maze alternation for APS vs control mice, P < 0.001) and behavioral changes (higher number of rears (18 +/- 2 vs 11 +/- 1, P < 0.006) and higher number of stairs climbed (12 +/- 2 vs 7 +/- 1, P < 0.02). This is the first report of cognitive deficits in this APS model and demonstrates the time course for the development of previously described behavioral changes. The mechanism involved in these CNS manifestations remains to be elucidated.