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Low-molecular-weight-heparin increases Th1-and Th17-associated chemokine levels during pregnancy in women with unexplained recurrent pregnancy loss: a randomised controlled trial
Malmo and Lund Univ, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Tor Vergata Univ Hosp, Italy; Tor Vergata Univ Hosp, Italy.
Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 12314Article in journal (Refereed) Published
Abstract [en]

Low-molecular-weight heparin (LMWH) is widely used to treat recurrent pregnancy loss (RPL) because of its anti-coagulant effects. Although in vitro studies have suggested additional immunological effects, these are debated. We therefore investigated whether LMWH could modulate immune responses in vivo during pregnancy of women with unexplained RPL. A Swedish open multi-centre randomised controlled trial included 45 women treated with tinzaparin and 42 untreated women. Longitudinally collected plasma samples were obtained at gestational weeks (gw) 6, 18, 28 and 34 and analysed by multiplex bead technology for levels of 11 cytokines and chemokines, chosen to represent inflammation and T-helper subset-associated immunity. Mixed linear models test on LMWH-treated and untreated women showed differences during pregnancy of the Th1-associated chemokines CXCL10 (p = 0.01), CXCL11 (p amp;lt; 0.001) and the Th17-associated chemokine CCL20 (p = 0.04), while CCL2, CCL17, CCL22, CXCL1, CXCL8, CXCL12, CXCL13 and IL-6 did not differ. Subsequent Students t-test showed significantly higher plasma levels of CXCL10 and CXCL11 in treated than untreated women at gw 28 and 34. The consistent increase in the two Th1-associated chemokines suggests a potential proinflammatory and unfavourable effect of LMWH treatment during later stages of pregnancy, when Th1 immunity is known to disrupt immunological tolerance.

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NATURE PUBLISHING GROUP , 2019. Vol. 9, article id 12314
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URN: urn:nbn:se:liu:diva-160163DOI: 10.1038/s41598-019-48799-6ISI: 000482396100028PubMedID: 31444404OAI: oai:DiVA.org:liu-160163DiVA, id: diva2:1349583
Note

Funding Agencies|Stig and Ragna Gorthon foundation, Helsingborg; Thelma Zoegas foundation for medical research, Lund; Medical Research Council of Southeast Sweden [FORSS-159721]; ALF grants, Region Ostergotland, Linkoping University; Skane County Councils Research and Development

Available from: 2019-09-09 Created: 2019-09-09 Last updated: 2019-11-27

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Bruno, ValentinaNedstrand, ElisabethBoij, RolandBerg, GöranSvensson Arvelund, JuditJenmalm, MariaRubér, MarieErnerudh, Jan
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Division of Neuro and Inflammation ScienceFaculty of Medicine and Health SciencesDivision of Children's and Women's healthDepartment of Gynaecology and Obstetrics in LinköpingDivision of Hematopoiesis and Developmental BiologyDepartment of Clinical Immunology and Transfusion Medicine
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