title: Immunomodulatory effects of therapeutic plasma exchange on monocytes in antiphospholipid syndrome.
abstract: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombosis and recurrent fetal loss, with the persistent presence of antiphospholipid antibodies (aPLs). aPLs exert their pathogenic effect via the overproduction of tissue factor and activation of complement and several cell types, including endothelial cells, platelets and notably monocytes. As a result, a hypercoagulable state develops leading to APS-associated obstetric complications and fetal loss. Despite being far from optimal, treatment of APS usually includes heparin and low dose aspirin. Recently, plasma exchange (PE) therapy was successfully used in patients with APS with obstetric complications who did not respond to the standard treatment. Therefore, the present study investigated the mechanism underlying PE action, and aimed to determine whether PE affects the functional activity of APS monocytes by examining the expression of 11 mRNA transcripts encoding cytokines, signaling molecules and transcription factors. Monocytes were collected prior to and following the PE treatment from women with APS who experienced recurrent pregnancy losses, as well as from healthy volunteers. Compared with control cells, APS monocytes showed deregulated expression of interleukin (IL)-1β, IL-6, IL-23, chemokine (C-C motif) ligand 2 (CCL2), C-X-C motif chemokine 10 (CXCL10), toll-like receptor 2, and signal transducer and activator of transcription 3. PE treatment resulted in increased IL-1β, IL-6, IL-23, CCL2, P2X7 and tumor necrosis factor-α mRNA transcripts in APS monocytes, restoring the mRNA expression levels to within normal ranges. Furthermore, PE therapy counterbalanced the expression levels of CCL2 and CXCL10, the levels of which are indicative of T helper cell 1/2 balance. The results of the present study indicate that the altered transcriptional profile in APS monocytes was restored by the immunomodulatory effect of plasmapheresis.
authors.affiliation: Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacky University, Olomouc 77520, Czech Republic; Group of Molecular and Cellular Immunology, Institute of Molecular Biology, National Academy of Sciences, Yerevan 0014, Armenia.
authors.forename: Anush
authors.initials: A
authors.lastname: Martirosyan
authors.affiliation: Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacky University, Olomouc 77520, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Petrek
authors.affiliation: Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacky University, Olomouc 77520, Czech Republic.
authors.forename: Amit
authors.initials: A
authors.lastname: Kishore
authors.affiliation: Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacky University, Olomouc 77520, Czech Republic; Group of Molecular and Cellular Immunology, Institute of Molecular Biology, National Academy of Sciences, Yerevan 0014, Armenia.
authors.forename: Gayane
authors.initials: G
authors.lastname: Manukyan
keywords: antiphospholipid syndrome; cytokines; mRNA; monocytes; therapeutic plasma exchange