{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:50:13Z","timestamp":1793393413381,"version":"4.5.0"},"reference-count":43,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2021,3,7]],"date-time":"2021-03-07T00:00:00Z","timestamp":1615075200000},"content-version":"unspecified","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Queen Victoria\u2019s Freemasons foundation"},{"name":"Ingegerd Johansson's donation"},{"DOI":"10.13039\/501100005689","name":"G\u00f6teborgs L\u00e4kares\u00e4llskap","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005689","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement"},{"DOI":"10.13039\/501100005390","name":"Alfred \u00d6sterlunds Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005390","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018740","name":"Anna-Greta Crafoord foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100018740","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003849","name":"IngaBritt och Arne Lundbergs Forskningsstiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003849","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003744","name":"Stiftelsen Handlanden Hjalmar Svenssons","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003744","id-type":"DOI","asserted-by":"publisher"}]},{"name":"King Gustaf V's 80th Anniversary foundation"},{"DOI":"10.13039\/100008448","name":"Rune och Ulla Aml\u00f6vs Stiftelse f\u00f6r Neurologisk och Reumatologisk Forskning","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008448","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009800","name":"Stiftelsen Professor Nanna Svartz Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009800","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007949","name":"Reumatikerf\u00f6rbundet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007949","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006285","name":"Magnus Bergvalls Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006285","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Lupus Sci Med"],"accepted":{"date-parts":[[2021,3,1]]},"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Women with SLE face an increased risk of adverse pregnancy outcomes compared with healthy women, but the underlying immunological mechanisms are unknown. Given the recognised association of neutrophil activation with SLE pathogenesis, we examined whether there is increased neutrophil activation and inflammation in blood and placenta in SLE relative to healthy pregnancy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>At delivery, peripheral blood, maternal-derived intervillous blood and placentas were collected from 12 SLE and 10 healthy control pregnancies. The proportion of low-density granulocytes (LDGs) and the activation status of LDG and normal-density granulocytes were examined with flow cytometry. The chemokines CXCL8 and CXCL1 were quantified with a cytometric bead-based assay and interferon alpha (IFN\u03b1) protein levels with a Simoa method. IFN\u03b1-stimulated maternal-derived decidual stromal cells were examined for <jats:italic>CXCL8<\/jats:italic> gene expression with qPCR. A pathologist, blinded to the patient background, examined all placentas.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Women with SLE had significantly higher proportions of LDG in peripheral blood compared with controls (p=0.02), and LDG in both peripheral and intervillous blood were more activated in SLE relative to healthy pregnancies (peripheral blood: p=0.002 and intervillous blood: p=0.05). There were higher levels of CXCL8 and CXCL1 in intervillous compared with peripheral blood in women with SLE (p=0.004 and p=&lt;0.0001, respectively) but not in controls. In SLE pregnancy, IFN\u03b1 was detectable in 6 out of 10 intervillous blood samples but only in one control. Stimulation with IFN\u03b1 upregulated <jats:italic>CXCL8<\/jats:italic> gene expression in decidual stromal cells from both SLE and healthy pregnancy. Histological chorioamnionitis was present in 6 out of 12 placentas from women with SLE and in 1 out of 10 controls.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In women with SLE, locally produced chemokines in the placenta are increased and may attract and activate neutrophils. This in turn could contribute to placental inflammation and dysfunction and increased risk of placenta-related pregnancy complications.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/lupus-2020-000463","type":"journal-article","created":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T11:05:13Z","timestamp":1615201513000},"page":"e000463","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":32,"title":["Activated low-density granulocytes in peripheral and intervillous blood and neutrophil inflammation in placentas from SLE pregnancies"],"prefix":"10.1136","volume":"8","author":[{"given":"Marit","family":"Stockfelt","sequence":"first","affiliation":[{"name":"Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunilla","family":"Larsson","sequence":"additional","affiliation":[{"name":"Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Engstr\u00f6m","sequence":"additional","affiliation":[{"name":"Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri","family":"Puttonen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Sahlgrenska University Hospital, Goteborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M\u00f6lndal, Sweden"},{"name":"UK Dementia Research, Institute at UCL, London, UK"},{"name":"Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M\u00f6lndal, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0900-2048","authenticated-orcid":false,"given":"Christopher","family":"Sj\u00f6wall","sequence":"additional","affiliation":[{"name":"Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Strevens","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sk\u00e5ne University Hospital, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"J\u00f6nsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders A","family":"Bengtsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Majczuk Sennstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Womens and Childrens Health, Division for Obstetrics and Gynecology, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agneta","family":"Zickert","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3396-3244","authenticated-orcid":false,"given":"Elisabet","family":"Svenungsson","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iva","family":"Gunnarsson","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Trysberg","sequence":"additional","affiliation":[{"name":"Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Jacobsson","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Goteborg, Sweden"},{"name":"Region V\u00e4stra G\u00f6taland, Sahlgrenska University Hospital, Department of Obstetrics and Gynecology, Gothenburg, Sweden"},{"name":"Department of Genetics and Bioinformatics, Domain of Health Data and Digitalisation, Institute of Public Health, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Karin","family":"Hultg\u00e5rd Ekwall","sequence":"additional","affiliation":[{"name":"Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Christenson","sequence":"additional","affiliation":[{"name":"Department of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy at the University of Gothenburg, Goteborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Bylund","sequence":"additional","affiliation":[{"name":"Department of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy at the University of Gothenburg, Goteborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattias N D","family":"Svensson","sequence":"additional","affiliation":[{"name":"Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4303-8266","authenticated-orcid":false,"given":"Anna-Carin","family":"Lundell","sequence":"additional","affiliation":[{"name":"Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2021,3,8]]},"reference":[{"key":"2025091511224480000_8.1.e000463.1","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/s41590-020-0677-6","article-title":"Autoimmunity and organ damage in systemic lupus erythematosus","volume":"21","author":"Tsokos","year":"2020","journal-title":"Nat Immunol"},{"key":"2025091511224480000_8.1.e000463.2","first-page":"1709","article-title":"Decrease in pregnancy loss rates in patients with systemic lupus erythematosus over a 40-year period","volume":"32","author":"Clark","year":"2005","journal-title":"J Rheumatol"},{"key":"2025091511224480000_8.1.e000463.3","doi-asserted-by":"crossref","unstructured":"WR H , Wei H . Maternal and fetal complications associated with systemic lupus erythematosus: an updated meta-analysis of the most recent studies (2017\u20132019). Medicine 2020;99.","DOI":"10.1097\/MD.0000000000019797"},{"key":"2025091511224480000_8.1.e000463.4","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1002\/acr.22791","article-title":"What to expect when expecting with systemic lupus erythematosus (SLE): a population-based study of maternal and fetal outcomes in SLE and Pre-SLE","volume":"68","author":"Arkema","year":"2016","journal-title":"Arthritis Care Res"},{"key":"2025091511224480000_8.1.e000463.5","doi-asserted-by":"crossref","DOI":"10.3390\/jcm9082598","article-title":"Adverse pregnancy outcomes after Multi-Professional follow-up of women with systemic lupus erythematosus: an observational study from a single centre in Sweden","volume":"9","author":"Saleh","year":"2020","journal-title":"J Clin Med"},{"key":"2025091511224480000_8.1.e000463.6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01300"},{"key":"2025091511224480000_8.1.e000463.7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02734"},{"key":"2025091511224480000_8.1.e000463.8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190185"},{"key":"2025091511224480000_8.1.e000463.9","doi-asserted-by":"publisher","DOI":"10.1136\/lupus-2015-000134"},{"key":"2025091511224480000_8.1.e000463.10","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780291105"},{"key":"2025091511224480000_8.1.e000463.11","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100450"},{"key":"2025091511224480000_8.1.e000463.12","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902199"},{"key":"2025091511224480000_8.1.e000463.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2015.08.040"},{"key":"2025091511224480000_8.1.e000463.14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031819"},{"key":"2025091511224480000_8.1.e000463.15","doi-asserted-by":"publisher","DOI":"10.1136\/lupus-2018-000270"},{"key":"2025091511224480000_8.1.e000463.16","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1002\/art.39029","article-title":"Interferon-\u03b1 and angiogenic dysregulation in pregnant lupus patients who develop preeclampsia","volume":"67","author":"Andrade","year":"2015","journal-title":"Arthritis Rheumatol"},{"key":"2025091511224480000_8.1.e000463.17","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1002\/art.40792","article-title":"Monitoring disease activity in systemic lupus erythematosus with single-molecule array digital enzyme-linked immunosorbent assay quantification of serum interferon-\u03b1","volume":"71","author":"Mathian","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"2025091511224480000_8.1.e000463.18","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-215571"},{"key":"2025091511224480000_8.1.e000463.19","doi-asserted-by":"publisher","DOI":"10.1002\/art.34473"},{"key":"2025091511224480000_8.1.e000463.20","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780400928"},{"key":"2025091511224480000_8.1.e000463.21","first-page":"288","article-title":"Systemic lupus erythematosus disease activity index 2000","volume":"29","author":"Gladman","year":"2002","journal-title":"J Rheumatol"},{"key":"2025091511224480000_8.1.e000463.22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1996.tb14164.x"},{"key":"2025091511224480000_8.1.e000463.23","unstructured":"Clair Evans PC . Tissue pathway for histopathological examination of the placenta. London: The Royal College of Pathologists, 2019."},{"key":"2025091511224480000_8.1.e000463.24","doi-asserted-by":"publisher","DOI":"10.1080\/14653240600855905"},{"key":"2025091511224480000_8.1.e000463.25","doi-asserted-by":"publisher","DOI":"10.1080\/10245330701214145"},{"key":"2025091511224480000_8.1.e000463.26","doi-asserted-by":"publisher","DOI":"10.1136\/lupus-2020-000399"},{"key":"2025091511224480000_8.1.e000463.27","doi-asserted-by":"publisher","DOI":"10.1136\/lupus-2020-000382"},{"key":"2025091511224480000_8.1.e000463.28","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e3181c2bde8"},{"key":"2025091511224480000_8.1.e000463.29","doi-asserted-by":"crossref","DOI":"10.1002\/JLB.3A0520-081RR","article-title":"The neutrophil subset defined by CD177 expression is preferentially recruited to gingival crevicular fluid in periodontitis","volume":"109","author":"Dahlstrand Rudin","year":"2021","journal-title":"J Leukoc Biol"},{"key":"2025091511224480000_8.1.e000463.30","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3RI0917-361R"},{"key":"2025091511224480000_8.1.e000463.31","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0141-8"},{"key":"2025091511224480000_8.1.e000463.32","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/imr.12448","article-title":"Human neutrophils in the saga of cellular heterogeneity: insights and open questions","volume":"273","author":"Scapini","year":"2016","journal-title":"Immunol Rev"},{"key":"2025091511224480000_8.1.e000463.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2003.08.027"},{"key":"2025091511224480000_8.1.e000463.34","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1111\/j.1447-0756.2007.00626.x","article-title":"Plasma levels of alpha-defensins 1-3 are an indicator of neutrophil activation in pregnant and post-partum women","volume":"33","author":"Okazaki","year":"2007","journal-title":"J Obstet Gynaecol Res"},{"key":"2025091511224480000_8.1.e000463.35","unstructured":"Bashant KR , Aponte AM , Randazzo D . Proteomic, biomechanical and functional analyses define neutrophil heterogeneity in systemic lupus erythematosus. Ann Rheum Dis 2020:annrheumdis-2020-218338."},{"key":"2025091511224480000_8.1.e000463.36","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.99276","article-title":"Neutrophil subsets and their gene signature associate with vascular inflammation and coronary atherosclerosis in lupus","volume":"3","author":"Carlucci","year":"2018","journal-title":"JCI Insight"},{"key":"2025091511224480000_8.1.e000463.37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1908576116"},{"key":"2025091511224480000_8.1.e000463.38","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-08-105965"},{"key":"2025091511224480000_8.1.e000463.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2006.03.002"},{"key":"2025091511224480000_8.1.e000463.40","doi-asserted-by":"crossref","first-page":"39904","DOI":"10.1038\/srep39904","article-title":"IFN type I and II induce BAFF secretion from human decidual stromal cells","volume":"7","author":"Lundell","year":"2017","journal-title":"Sci Rep"},{"key":"2025091511224480000_8.1.e000463.41","first-page":"339","article-title":"Pathology findings in preterm placentas of women with autoantibodies: a case-control study","volume":"11","author":"Locatelli","year":"2002","journal-title":"J Matern Fetal Neonatal Med"},{"key":"2025091511224480000_8.1.e000463.42","doi-asserted-by":"publisher","DOI":"10.1155\/S1064744997000471"},{"key":"2025091511224480000_8.1.e000463.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2004.10.003"}],"container-title":["Lupus Science &amp; Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/lupus-2020-000463","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T18:22:57Z","timestamp":1757960577000},"score":1,"resource":{"primary":{"URL":"https:\/\/lupus.bmj.com\/lookup\/doi\/10.1136\/lupus-2020-000463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,3,8]]},"published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1136\/lupus-2020-000463"],"URL":"https:\/\/doi.org\/10.1136\/lupus-2020-000463","relation":{},"ISSN":["2053-8790"],"issn-type":[{"value":"2053-8790","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3]]}}}