Antiphosphatidylethanolamine Antibodies and Deep Vein Thrombosis in Lupus Patients with Antiphospholipid Syndrome

Backgroud. Which factors determine venous thrombotic events in some antiphospholipid syndrome (APS) patients and arterial thrombosis or conditions related to pregnancy in others has not been established yet. Purpose. The aim of this study was to search the antiphospholipid antibodies (APLAs) correlates in regard to deep vein thrombosis (DVT) in patients with systemic lupus erythematosus (SLE) and APS. Methods. Twenty-nine patients fulfilling the criteria of both SLE and APS were included. Complete anamnesis and clinical examination was performed on inclusion. Also, for all patients, disease activity was assessed by the SLEDAI score. An extended APLAs profile, ten Abs, was searched. Results. The titers of IgG anticardiolipin (aCL), IgG anti-β2 glycoprotein I (aβ2GPI), IgG antiphosphatidylethanolamine (aPE), and also of IgG antiprothrombin (aPT) were significant higher in patients with DVT history. After analysis by ROC curve and univariate logistic regression, the strongest association was found for IgG aPE. Also, in multivariate analysis, SLEDAI score correlated with the DVT antecedents. Conclusions. IgG aPE might be involved in DVT pathogenic pathways in patients with SLE and APS as their titers remain significantly higher in patients with previous DVT. Lupus patients with DVT events represent a subgroup of patients with more severe underlying pathology.

Early endosome as a pathogenic target for antiphosphatidylethanolamine antibodies

Phosphatidylethanolamine (PE) is a major phospholipid species with important roles in membrane trafficking and reorganization. Accumulating clinical data indicate that the presence of circulating antibodies against PE is positively correlated with the symptoms of antiphospholipid syndromes (APS), including thrombosis and repeated pregnancy loss. However, PE is generally sequestered inside a normal resting cell, and the mechanism by which circulating anti-PE antibodies access cellular PE remains unknown. The studies presented here were conducted with synthetic PE-binding agents, plasma samples from patients with anti-PE autoimmunity, and purified anti-PE antibodies. The results suggest that the cellular vulnerability to anti-PE antibodies may be mediated by the binding of PE molecules in the membrane of the early endosome. Endosomal PE binding led to functional changes in endothelial cells, including declines in proliferation and increases in the production of reactive oxygen species, as well as the expression of inflammatory molecules. Collectively, our findings provide insight into the etiology of anti-PE autoimmunity and, because endosomes are of central importance in almost all types of cells, could have important implications for a wide range of biological processes.

FACTORS ASSOCIATED WITH THE DEEP VEIN THROMBOSIS IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME

Introduction. Patients with antiphospholipid syndrome (APS) may have a large spectrum of thrombotic clinical events (arterial or venous), but the factors that determine the occurrence of specific clinical manifestation has not been clearly established. Objective. The aim of the study was to determine the factors associated with a history of deep vein thrombosis (DVT) in patients with APS. We were especially interested to fi nd an association between the criteria and non-criteria antiphospholipid antibodies (APLAs) and the DVT. Methods. We realized a cross-sectional study, with consecutive enrollment of all patients presented in our department with the diagnosis of APS in the period 2008-2011. From the total of 106 patients for which the demographic, clinical and biological parameters were collected, the assessment of the criteria and non-criteria APLAs was performed in 73 patients. Results. The mean age at inclusion was 44.7 years, the female-to-male ratio 6.6, and the mean APS disease duration 6.7 years. The majority of the patients included presented with secondary APS (70 patients). Lupus anticoagulant was the most frequent immunological marker used to sustain the diagnosis of APS, found positive in 102 patients (96.2%). The recurrent DVT was more frequently observed in patients with primary APS than in those with secondary APS (p = 0.02). No significant association with DVT was found for the clinical parameters traditionally associated with the risk of thrombosis that we have taken into study: smoking, body mass index (BMI), waist circumference and waist-to-hip ratio. We found a positive association between the DVT history and the positivity for the IgM anti-β2 glycoprotein I antibodies [OR (95%CI) = 6.95 (1.36-35.58), p = 0.01]. The titer of IgG antiprothrombin antibodies and IgG antiphosphatidylethanolamine antibodies was higher in patients with previous DVT [3.0 (0.0-151.0) versus 2.0 (0.0-2.0), p = 0.01, respectively 5.0 (1.0-33.0) versus 3.0 (1.0-7.0), p = 0.01]. In the subgroup of patients with secondary APS, the previous DVT was associated only with the positivity for IgM anti-β2 glycoprotein I antibodies [OR (95%) = 13.63 (1.46-127.15), p = 0.02]. In the same subgroup, the levels of IgG anticardiolipin and the IgG antiphosphatidylethanolamine antibodies were higher in patients with previous DVT [2.0 (0.0-64.0) versus 1.0 (0.0-20.0), p = 0.02, respectively 3.0 (0.0-151.0) versus 2.0 (0.0-7.0), p = 0.03]. In patients with primary APS, the titer of IgG antiprothrombin antibodies was significantly higher when DVT history were present [5.0 (1.0-3.0) versus 3.0 (1.0-7.0), p = 0.01. Only the titer of IgG antiprothrombin antibodies was associated with the history of recurrent thrombosis [5.0 (1.0-3.0) versus 3.0 (1.0-7.0), p = 0.01]. Conclusions. In patients with APS, the DVT history was related with the prevalence of the anti-β2 glycoprotein I antibodies, but also with the levels of some non-criteria antibodies, IgG antiprothrombin antibodies and IgG antiphosphatidylethanolamine antibodies. In patients with primary APS, previous DVT is associated only with the titer of IgG antiprothrombin antibodies, whereas in patients with secondary APS, the DVT history were related with the presence of anti-β2 glycoprotein I antibodies and with the titers of both criteria antibodies (IgG anticardiolipin antibodies) and non-criteria antibodies (IgG antiphosphatidylethanolamine antibodies). The risk of recurrent thrombosis was higher in patients with primary APS when compared with those with secondary APS. Only the titers of IgG antiprothrombin antibodies were correlated with recurrent thrombosis.