Martirosyan Anush, Petrek Martin, Kishore Amit, Manukyan Gayane
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.
Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacky University, Olomouc 77520, Czech Republic.
Exp Ther Med. 2016 Aug;12(2):1189-1195. doi: 10.3892/etm.2016.3441. Epub 2016 Jun 8.
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.
抗磷脂综合征（APS）是一种全身性自身免疫性疾病，其特征为血栓形成和反复流产，并持续存在抗磷脂抗体（aPLs）。aPLs通过组织因子的过度产生以及补体和几种细胞类型（包括内皮细胞、血小板，尤其是单核细胞）的激活发挥其致病作用。结果，形成高凝状态，导致与APS相关的产科并发症和流产。尽管远非理想，但APS的治疗通常包括肝素和低剂量阿司匹林。最近，血浆置换（PE）疗法成功用于对标准治疗无反应的伴有产科并发症的APS患者。因此，本研究调查了PE作用的潜在机制，旨在通过检测编码细胞因子、信号分子和转录因子的11种mRNA转录本的表达，确定PE是否影响APS单核细胞的功能活性。从经历反复妊娠丢失的APS女性以及健康志愿者中，在PE治疗前后收集单核细胞。与对照细胞相比，APS单核细胞显示白细胞介素（IL）-1β、IL-6、IL-23、趋化因子（C-C基序）配体2（CCL2）、C-X-C基序趋化因子10（CXCL10）、Toll样受体2以及信号转导和转录激活因子3的表达失调。PE治疗导致APS单核细胞中IL-1β、IL-6、IL-23、CCL2、P2X7和肿瘤坏死因子-α mRNA转录本增加，使mRNA表达水平恢复到正常范围内。此外，PE疗法平衡了CCL2和CXCL10的表达水平，其水平指示辅助性T细胞1/2平衡。本研究结果表明，血浆置换的免疫调节作用恢复了APS单核细胞中改变的转录谱。
