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.

Anti-domain 1 β2 glycoprotein antibodies increase expression of tissue factor on monocytes and activate NK Cells and CD8+ cells in vitro

“…The direct pathogenic role of aPL antibodies was demonstrated in animal models showing pregnancy loss and thrombus formation after the immunisation of animals with aPLs [45,46]. Another proof is evidence of the clinical improvement after the removal of autoantibodies by plasma exchange or plasmapheresis [47,48]. Our study shows the ability of patient-derived aPL to induce immune cell activation and contribute to the thrombotic events.…”

Therapeutic plasma exchange versus double plasma molecular absorption system in hepatitis B virus‐infected acute‐on‐chronic liver failure treated by entercavir: A prospective study

“…Data on the effect of ALSSs on serum IL‐6 levels are controversial. Previous studies reported that TPE reduced the elevated serum levels of IL‐6 in patients with ALF, Martirosyan et al showed that TPE increased IL‐6 mRNA transcripts in monocytes from patients with antiphosphalipid syndrome, restoring the mRNA expression levels to within normal ranges, whereas Vanessa et al showed that FPSA and MARS failed to change serum IL‐6 levels significantly in patients with ACLF despite IL‐6 was removed by the two systems, and the discrepancy was probably due to a high rate of cytokine production in ACLF patients . However, few studies investigated the effect of TPE and DPMAS on serum levels of IL‐6 in ACLF patients.…”

Environmental Triggers of Autoreactive Responses: Induction of Antiphospholipid Antibody Formation

“…Another evidence for the pathogenicity of autoantibodies was obtained in studies proving a substantial clinical improvement after the removal of autoantibodies by plasma exchange or plasmapheresis (8). Mechanistically, we demonstrated the restoration of monocyte transcriptional activity in patients with APS after plasmapheresis (9).…”