PROTEOMIC ANALYSIS OF BIOLOGICAL MATERIAL FROM WOMEN WITH ANTIPHOSPHOLIPID SYNDROME. A RETROSPECTIVE STUDY.

Objective. During the last decade, the role of complement system activation in the pathogenesis of antiphospholipid syndrome (APS) has been debated but an evident correlation with the proinflammatory and procoagulant phenotype in this disease has never been found. We carried out a retrospective study on APS women to evaluate the expression of some soluble and local complement and coagulation molecules supposed to be involved in promoting thrombotic events and pregnancy-related clinical complications.Methods. Complement C5a and C5b-9 complex, Tissue Factor (TF) and Tissue Factor Pathway Inhibitor (TFPI) plasma levels of APS patients and matched healthy women were analyzed by ELISA assays. Placenta samples of APS patients and controls were subjected to immunoblotting analysis with specific antibodies for complement component 5a Receptor (C5aR), CD46 (MCP, Membrane Cofactor Protein), CD55 (DAF, Decay Accelerating Factor), CD59, p-selectin, TF and TFPI. Mutations and polymorphisms analysis in the complement regulator genes were also performed. Results. In APS patients, both in pregnant and non-pregnant conditions, we found higher plasma levels of C5a, C5b-9 and TF compared to healthy subjects. In APS placenta, C5aR, C5b-9 and p-selectin levels were higher than in controls, conversely, CD46, CD55 and CD59 levels were lower compared to healthy subjects. Since clinical management of pregnancy in APS requires anticoagulant therapy (heparin), plasma and placenta content of TF and TFPI were affected by this treatment. In APS placenta donors, we did not find mutations or allele variances in the CD46, CD55 and CD59 genes.Conclusions. Our data suggest complement activation both in pregnant and non-pregnant APS patients as supported by the increase in key molecules from complement system. In this study, higher levels of activated complement molecules were associated to a proinflammatory and procoagulant state in APS subjects. The lower placental CD46, CD55 and CD59 expression may impair local protection, favoring local complement hyperactivation and leading to inflammation, thrombosis, tissue damage and possible fetal death, but further studies are necessary to better understand the mechanisms involved in complement dysregulation in APS syndrome.