{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:10:35Z","timestamp":1789013435202,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100013342","name":"NIHR Imperial Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013342","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Inflammation contributes to primary antiphospholipid syndrome (PAPS) pathogenesis, but cytokine profiles and associated thrombotic phenotypes remain incompletely defined. A panel of 20 cytokines, chemokines and endothelial activation markers was analysed in 37 PAPS patients on stable anticoagulation and 12 healthy controls (HC). We compared concentrations between groups and performed unsupervised hierarchical clustering and principal component analysis (PCA) to identify inflammatory subgroups. Compared with HC, patients with PAPS exhibited significantly elevated levels of 14\/20 analytes: granulocyte\u2010macrophage colony\u2010stimulating factor (GM\u2010CSF), interferon (IFN)\u2010\u03b3, interleukin (IL)\u20101\u03b1, IL\u20101\u03b2, IL\u20106, IL\u201010, IL\u201012p70, IL\u201013, IL\u201017a, tumour necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), intercellular adhesion molecule\u20101 (ICAM\u20101), P\u2010selectin and macrophage inflammatory protein\u20101\u03b2 (MIP1\u03b2) (all\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Unsupervised clustering identified three inflammatory antiphospholipid syndrome (APS) subgroups distinct from HC. A core cytokine signature comprising GM\u2010CSF, IL\u20106, IL\u201010, IL\u201012p70, IL\u201013 and TNF\u2010\u03b1 was elevated across all APS clusters. One cluster, enriched for arterial thrombosis, demonstrated a more pronounced inflammatory phenotype, with increased IFN\u2010\u03b1. Comparison of phenotypes showed significantly higher concentrations of GM\u2010CSF, IFN\u2010\u03b1, IL\u20101\u03b1, IL\u20104, IL\u20106, IL\u201010, IL\u201017a and TNF\u2010\u03b1 in arterial versus venous thrombosis. Our findings demonstrate widespread cytokine dysregulation and distinct inflammatory subgroups in PAPS, with arterial thrombosis showing stronger inflammation than venous thrombosis, supporting divergent thrombo\u2010inflammatory mechanisms and potential precision immunomodulatory therapeutic targets.\n                  <\/jats:p>","DOI":"10.1111\/bjh.70816","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:56:56Z","timestamp":1789012616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A pro\u2010inflammatory cytokine signature characterises thrombotic antiphospholipid syndrome despite stable anticoagulation"],"prefix":"10.1111","author":[{"given":"Catherine B.","family":"Ducker","sequence":"first","affiliation":[{"name":"Centre for Haematology, Department of Immunology and Inflammation Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1661-9889","authenticated-orcid":false,"given":"Megan V.","family":"Preece","sequence":"additional","affiliation":[{"name":"Centre for Haematology, Department of Immunology and Inflammation Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2761-913X","authenticated-orcid":false,"given":"Jeremy","family":"Schofield","sequence":"additional","affiliation":[{"name":"Department of Clinical Infection, Microbiology and Immunology University of Liverpool  Liverpool UK"},{"name":"Roald Dahl Haemostasis and Thrombosis Centre Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8804-0493","authenticated-orcid":false,"given":"Charis","family":"Pericleous","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8268-3268","authenticated-orcid":false,"given":"Mike","family":"Laffan","sequence":"additional","affiliation":[{"name":"Centre for Haematology, Department of Immunology and Inflammation Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3949-2455","authenticated-orcid":false,"given":"Simon","family":"Abrams","sequence":"additional","affiliation":[{"name":"Department of Clinical Infection, Microbiology and Immunology University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5993-4850","authenticated-orcid":false,"given":"Deepa J.","family":"Arachchillage","sequence":"additional","affiliation":[{"name":"Centre for Haematology, Department of Immunology and Inflammation Imperial College London  London UK"},{"name":"Department of Haematology Imperial College Healthcare NHS Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"issue":"3","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1111\/bjh.19635","article-title":"Guidelines on the investigation and management of antiphospholipid syndrome","volume":"205","author":"Arachchillage DJ","year":"2024","journal-title":"Br J Haematol"},{"issue":"3","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","DOI":"10.3390\/jcm14030733","article-title":"Antiphospholipid syndrome: a comprehensive clinical review","volume":"14","author":"Patriarcheas V","year":"2025","journal-title":"J Clin Med"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/978-3-540-29805-2_986","volume-title":"Encyclopedia of Pain","author":"Wallace V","year":"2007"},{"key":"e_1_2_10_5_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2025.1527554","article-title":"Mechanism of antiphospholipid antibody\u2010mediated thrombosis in antiphospholipid syndrome","volume":"16","author":"Yang L","year":"2025","journal-title":"Front Immunol"},{"issue":"4","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.2174\/1570161115666170105120931","article-title":"Thrombotic Management of Antiphospholipid Syndrome: towards novel targeted therapies","volume":"15","author":"Islam MA","year":"2017","journal-title":"Curr Vasc Pharmacol"},{"issue":"4","key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1007\/s11239-020-02155-y","article-title":"Inflammatory markers in thrombosis associated with primary antiphospholipid syndrome","volume":"50","author":"Arantes FT","year":"2020","journal-title":"J Thromb Thrombolysis"},{"issue":"9","key":"e_1_2_10_8_1","article-title":"Cytokine profiles in antiphospholipid syndrome [abstract]","volume":"77","author":"Liu XG","year":"2025","journal-title":"Arthritis Rheumatol"},{"issue":"11","key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"2828","DOI":"10.1111\/jth.15047","article-title":"Guidance from the scientific and standardization committee for lupus anticoagulant\/antiphospholipid antibodies of the international society on thrombosis and Haemostasis: update of the guidelines for lupus anticoagulant detection and interpretation","volume":"18","author":"Devreese KMJ","year":"2020","journal-title":"J Thromb Haemost"},{"key":"e_1_2_10_10_1","volume-title":"_R: a language and environment for statistical computing","author":"R Core Team","year":"2025"},{"key":"e_1_2_10_11_1","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-24277-4","volume-title":"ggplot2: elegant graphics for data analysis","author":"Wickham H","year":"2016"},{"key":"e_1_2_10_12_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v021.i12","article-title":"Reshaping data with the reshape package","volume":"21","author":"Wickham H","year":"2007","journal-title":"J Stat Softw"},{"key":"e_1_2_10_13_1","unstructured":"LucasA.amap: another multidimensional analysis package. R package version 0.8\u201020.2024. Available from:https:\/\/CRAN.R\u2010project.org\/package=amap"},{"key":"e_1_2_10_14_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.blre.2026.101364","article-title":"Revisiting antiphospholipid syndrome: a thrombo\u2010inflammatory disorder beyond clotting","volume":"76","author":"Ducker CB","year":"2026","journal-title":"Blood Rev"},{"issue":"7","key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1046\/j.1538-7836.2003.00261.x","article-title":"Inflammation and thrombosis","volume":"1","author":"Esmon CT","year":"2003","journal-title":"J Thromb Haemost"},{"issue":"1","key":"e_1_2_10_16_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.rpth.2024.102665","article-title":"A cell\u2010based model to study mechanisms of endothelial\u2010dependent thrombin generation in response to inflammation and its modulation by hydroxychloroquine","volume":"9","author":"Arachchillage DJ","year":"2025","journal-title":"Res Pract Thromb Haemost"},{"issue":"11","key":"e_1_2_10_17_1","doi-asserted-by":"crossref","DOI":"10.3390\/cells14110766","article-title":"IL\u20106 as a mediator of platelet hyper\u2010responsiveness","volume":"14","author":"Webb CE","year":"2025","journal-title":"Cells"},{"key":"e_1_2_10_18_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.888763","article-title":"The Th17 pathway in vascular inflammation: culprit or consort?","volume":"13","author":"Robert M","year":"2022","journal-title":"Front Immunol"},{"key":"e_1_2_10_19_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.873644","article-title":"Preliminary study on the imbalance between Th17 and regulatory T cells in antiphospholipid syndrome","volume":"13","author":"Yan H","year":"2022","journal-title":"Front Immunol"},{"key":"e_1_2_10_20_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2019.00487","article-title":"Type I interferon signature in primary antiphospholipid syndrome: clinical and laboratory associations","volume":"10","author":"Palli E","year":"2019","journal-title":"Front Immunol"},{"key":"e_1_2_10_21_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaut.2022.102978","article-title":"Whole blood transcriptome identifies interferon\u2010regulated genes as key drivers in thrombotic primary antiphospholipid syndrome","volume":"134","author":"Verrou KM","year":"2023","journal-title":"J Autoimmun"},{"issue":"18","key":"e_1_2_10_22_1","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.93897","article-title":"Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target","volume":"2","author":"Knight JS","year":"2017","journal-title":"JCI Insight"},{"issue":"7","key":"e_1_2_10_23_1","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1136\/annrheumdis-2013-204600","article-title":"Gene profiling reveals specific molecular pathways in the pathogenesis of atherosclerosis and cardiovascular disease in antiphospholipid syndrome, systemic lupus erythematosus and antiphospholipid syndrome with lupus","volume":"74","author":"Perez\u2010Sanchez C","year":"2015","journal-title":"Ann Rheum Dis"},{"issue":"4","key":"e_1_2_10_24_1","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.autrev.2018.11.004","article-title":"Enhanced type I interferon gene signature in primary antiphospholipid syndrome: association with earlier disease onset and preeclampsia","volume":"18","author":"Ugolini\u2010Lopes MR","year":"2019","journal-title":"Autoimmun Rev"},{"issue":"3","key":"e_1_2_10_25_1","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1093\/rheumatology\/keac466","article-title":"Antiphospholipid antibodies in patients with calcific aortic valve stenosis","volume":"62","author":"Plunde O","year":"2023","journal-title":"Rheumatology (Oxford)"},{"key":"e_1_2_10_26_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jtauto.2023.100202","article-title":"Antiphospholipid antibodies induce proinflammatory and procoagulant pathways in endothelial cells","volume":"6","author":"Patsouras M","year":"2023","journal-title":"J Transl Autoimmun"},{"key":"e_1_2_10_27_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2025.1676578","article-title":"A proteomic map of thromboinflammatory signatures in antiphospholipid syndrome: results from antiphospholipid syndrome alliance for clinical trials and international networking (APS ACTION) registry","volume":"16","author":"Pine A","year":"2025","journal-title":"Front Immunol"},{"key":"e_1_2_10_28_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.blre.2020.100788","article-title":"Arterial thrombosis in antiphospholipid syndrome (APS): clinical approach and treatment. A systematic review","volume":"48","author":"Cheng C","year":"2021","journal-title":"Blood Rev"},{"issue":"1","key":"e_1_2_10_29_1","doi-asserted-by":"crossref","first-page":"3682","DOI":"10.1182\/blood-2019-127601","article-title":"Study of the role of Hydroxychloroquine in immunomodulation and control of hypercoagulability in patients diagnosed with primary antiphospholipid syndrome","volume":"134","author":"Mangolin S","year":"2019","journal-title":"Blood"},{"issue":"3","key":"e_1_2_10_30_1","doi-asserted-by":"crossref","first-page":"H969","DOI":"10.1152\/ajpheart.00400.2008","article-title":"Leukocyte\u2010endothelial cell interactions are linked to vascular permeability via ICAM\u20101\u2010mediated signaling","volume":"295","author":"Sumagin R","year":"2008","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"2","key":"e_1_2_10_31_1","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/1529-0131(199802)41:2<224::AID-ART6>3.0.CO;2-W","article-title":"Ciprofloxacin immunomodulation of experimental antiphospholipid syndrome associated with elevation of interleukin\u20103 and granulocyte\u2010macrophage colony\u2010stimulating factor expression","volume":"41","author":"Blank M","year":"1998","journal-title":"Arthritis Rheum"},{"issue":"6","key":"e_1_2_10_32_1","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/S0015-0282(00)00533-1","article-title":"Interleukin\u20103 and human trophoblast: in\u00a0vitro explanations for the effect of interleukin in patients with antiphospholipid antibody syndrome","volume":"73","author":"Di Simone N","year":"2000","journal-title":"Fertil Steril"},{"issue":"2","key":"e_1_2_10_33_1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/j.1538-7836.2009.03674.x","article-title":"Clinical course of high\u2010risk patients diagnosed with antiphospholipid syndrome","volume":"8","author":"Pengo V","year":"2010","journal-title":"J Thromb Haemost"},{"issue":"1","key":"e_1_2_10_34_1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1182\/blood-2022-166074","article-title":"Anticoagulation practice, recurrent thrombosis, and major bleeding in antiphospholipid syndrome\u2010 a multicentre observational study in the United Kingdom","volume":"140","author":"Crossette\u2010Thambiah C","year":"2022","journal-title":"Blood"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.70816","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bjh.70816","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.70816","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:57:03Z","timestamp":1789012623000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.70816"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":33,"alternative-id":["10.1111\/bjh.70816"],"URL":"https:\/\/doi.org\/10.1111\/bjh.70816","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]},"assertion":[{"value":"2026-06-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"bjh.70816"}}