{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:46:23Z","timestamp":1788345983465,"version":"build-2803163510"},"reference-count":93,"publisher":"American Society of Hematology","issue":"6","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,2,6]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Thromboembolic complication is common in severe coronavirus disease 2019 (COVID-19), leading to an investigation into the presence of prothrombotic antibodies akin to those found in heparin-induced thrombocytopenia (HIT). In a study of samples from 130 hospitalized patients, collected 3.6 days after COVID-19 diagnosis, 80% had immunoglobulin G (IgG) antibodies recognizing complexes of heparin and platelet factor 4 (PF4; PF4\/H), and 41% had antibodies inducing PF4-dependent P-selectin expression in CpG oligodeoxynucleotide\u2013treated normal platelets. Unlike HIT, both PF4\/H-reactive and platelet-activating antibodies were found in patients with COVID-19 regardless of recent heparin exposure. Notably, PF4\/H-reactive IgG antibodies correlated with those targeting the receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 spike protein. Moreover, introducing exogenous RBD to or removing RBD-reactive IgG from COVID-19 plasma or IgG purified from COVID-19 plasma significantly reduced their ability to activate platelets. RBD-specific antibodies capable of platelet activation were cloned from peripheral blood B cells of patients with COVID-19. These antibodies possessed sequence motifs in the heavy-chain complementarity-determining region 3 (HCDR3), resembling those identified in pathogenic HIT antibodies. Furthermore, IgG+ B cells having these HCDR3 signatures were markedly expanded in patients with severe COVID-19. Importantly, platelet-activating antibodies present in patients with COVID-19 were associated with a specific elevation of platelet \u03b1-granule proteins in the plasma and showed a positive correlation with markers for inflammation and tissue damage, suggesting a functionality of these antibodies in patients. The demonstration of functional and structural similarities between certain RBD-specific antibodies in patients with COVID-19 and pathogenic antibodies typical of HIT suggests a novel mechanism by which RBD-specific antibodies might contribute to thrombosis in COVID-19.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2024025010","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T22:00:57Z","timestamp":1732312857000},"page":"635-647","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":5,"title":["Prothrombotic antibodies targeting the spike protein's receptor-binding domain in severe COVID-19"],"prefix":"10.1182","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7734-9943","authenticated-orcid":false,"given":"Wen","family":"Zhu","sequence":"first","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"},{"name":"2Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1947-5386","authenticated-orcid":false,"given":"Yongwei","family":"Zheng","sequence":"additional","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Yu","sequence":"additional","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2770-4522","authenticated-orcid":false,"given":"Nathan","family":"Witman","sequence":"additional","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"},{"name":"2Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1236-8478","authenticated-orcid":false,"given":"Lu","family":"Zhou","sequence":"additional","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"},{"name":"2Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Wei","sequence":"additional","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"},{"name":"3Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5459-1131","authenticated-orcid":false,"given":"Yongguang","family":"Zhang","sequence":"additional","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"},{"name":"3Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3902-7652","authenticated-orcid":false,"given":"Paytsar","family":"Topchyan","sequence":"additional","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"},{"name":"2Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5750-8134","authenticated-orcid":false,"given":"Christine","family":"Nguyen","sequence":"additional","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"},{"name":"2Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4572-6955","authenticated-orcid":false,"given":"David","family":"Wang","sequence":"additional","affiliation":[{"name":"4School of Art and Science Undergraduate Program, Washington University in St. Louis, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0467-8308","authenticated-orcid":false,"given":"Rae","family":"Janecke","sequence":"additional","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2519-4377","authenticated-orcid":false,"given":"Anand","family":"Padmanabhan","sequence":"additional","affiliation":[{"name":"5Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1171-0548","authenticated-orcid":false,"given":"Lisa","family":"Baumann Kreuziger","sequence":"additional","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"},{"name":"6Division of Hematology Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert C.","family":"White","sequence":"additional","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8800-297X","authenticated-orcid":false,"given":"Parameswaran","family":"Hari","sequence":"additional","affiliation":[{"name":"6Division of Hematology Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8379-0962","authenticated-orcid":false,"given":"Tongjun","family":"Gu","sequence":"additional","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander T.","family":"Fields","sequence":"additional","affiliation":[{"name":"7Department of Surgery, University of California San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1861-9691","authenticated-orcid":false,"given":"Lucy Z.","family":"Kornblith","sequence":"additional","affiliation":[{"name":"7Department of Surgery, University of California San Francisco, San Francisco, CA"},{"name":"8Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0811-7214","authenticated-orcid":false,"given":"Richard","family":"Aster","sequence":"additional","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"},{"name":"6Division of Hematology Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4508-4263","authenticated-orcid":false,"given":"Jieqing","family":"Zhu","sequence":"additional","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"},{"name":"9Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1562-9218","authenticated-orcid":false,"given":"Weiguo","family":"Cui","sequence":"additional","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"},{"name":"2Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI"},{"name":"10Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7878-6101","authenticated-orcid":false,"given":"Shawn","family":"Jobe","sequence":"additional","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"},{"name":"11Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9207-8176","authenticated-orcid":false,"given":"Mary Beth","family":"Graham","sequence":"additional","affiliation":[{"name":"12Division of Infectious Disease, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5549-3795","authenticated-orcid":false,"given":"Demin","family":"Wang","sequence":"additional","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"},{"name":"2Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2420-8212","authenticated-orcid":false,"given":"Renren","family":"Wen","sequence":"additional","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"},{"name":"2Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"13","key":"2025032119474670400_bib1","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1001\/jama.2020.2648","article-title":"Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention","volume":"323","author":"Wu","year":"2020","journal-title":"JAMA"},{"issue":"3","key":"2025032119474670400_bib2","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/s41569-020-00469-1","article-title":"Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation","volume":"18","author":"Gu","year":"2021","journal-title":"Nat Rev Cardiol"},{"issue":"10229","key":"2025032119474670400_bib3","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","article-title":"Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study","volume":"395","author":"Zhou","year":"2020","journal-title":"Lancet"},{"issue":"9","key":"2025032119474670400_bib4","doi-asserted-by":"crossref","first-page":"e671","DOI":"10.1016\/S2352-3026(20)30217-9","article-title":"Haematological characteristics and risk factors in the classification and prognosis evaluation of COVID-19: a retrospective cohort study","volume":"7","author":"Liao","year":"2020","journal-title":"Lancet Haematol"},{"issue":"6","key":"2025032119474670400_bib5","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1097\/CRD.0000000000000330","article-title":"Elevated D-dimer levels are associated with increased risk of mortality in COVID-19: a systematic review and meta-analysis","volume":"28","author":"Shah","year":"2020","journal-title":"Cardiol Rev"},{"issue":"4","key":"2025032119474670400_bib6","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1111\/jth.14768","article-title":"Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia","volume":"18","author":"Tang","year":"2020","journal-title":"J\u00a0Thromb Haemost"},{"issue":"18","key":"2025032119474670400_bib7","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical characteristics of coronavirus disease 2019 in China","volume":"382","author":"Guan","year":"2020","journal-title":"N\u00a0Engl J Med"},{"issue":"11","key":"2025032119474670400_bib8","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1182\/blood.2020007214","article-title":"Platelet gene expression and function in COVID-19 patients","volume":"136","author":"Manne","year":"2020","journal-title":"Blood"},{"issue":"8","key":"2025032119474670400_bib9","doi-asserted-by":"crossref","first-page":"e575","DOI":"10.1016\/S2352-3026(20)30216-7","article-title":"Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study","volume":"7","author":"Goshua","year":"2020","journal-title":"Lancet Haematol"},{"issue":"6","key":"2025032119474670400_bib10","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/s41577-020-0331-4","article-title":"Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages","volume":"20","author":"Merad","year":"2020","journal-title":"Nat Rev Immunol"},{"issue":"10","key":"2025032119474670400_bib11","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1182\/blood.2020007008","article-title":"Neutrophil extracellular traps (NETs) contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome","volume":"136","author":"Middleton","year":"2020","journal-title":"Blood"},{"issue":"2","key":"2025032119474670400_bib12","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1056\/NEJMoa2015432","article-title":"Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19","volume":"383","author":"Ackermann","year":"2020","journal-title":"N\u00a0Engl J Med"},{"issue":"4","key":"2025032119474670400_bib13","doi-asserted-by":"crossref","first-page":"268","DOI":"10.7326\/M20-2003","article-title":"Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study","volume":"173","author":"Wichmann","year":"2020","journal-title":"Ann Intern Med"},{"issue":"21","key":"2025032119474670400_bib14","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.1182\/blood-2016-11-709873","article-title":"Heparin-induced thrombocytopenia","volume":"129","author":"Arepally","year":"2017","journal-title":"Blood"},{"issue":"3","key":"2025032119474670400_bib15","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1002\/(SICI)1096-8652(199703)54:3<196::AID-AJH4>3.0.CO;2-R","article-title":"Characterization of the humoral immune response in heparin-induced thrombocytopenia","volume":"54","author":"Suh","year":"1997","journal-title":"Am J Hematol"},{"issue":"2","key":"2025032119474670400_bib16","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1182\/blood-2013-01-478966","article-title":"Complex formation with nucleic acids and aptamers alters the antigenic properties of\u00a0platelet factor 4","volume":"122","author":"Jaax","year":"2013","journal-title":"Blood"},{"issue":"1","key":"2025032119474670400_bib17","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1182\/bloodadvances.2016000877","article-title":"Polyphosphate\/platelet factor 4 complexes can mediate heparin-independent platelet activation in heparin-induced thrombocytopenia","volume":"1","author":"Cines","year":"2016","journal-title":"Blood Adv"},{"issue":"6","key":"2025032119474670400_bib18","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/ajh.24006","article-title":"The platelet serotonin-release assay","volume":"90","author":"Warkentin","year":"2015","journal-title":"Am J Hematol"},{"issue":"8","key":"2025032119474670400_bib19","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1182\/blood.2020008195","article-title":"A\u00a0prospective, blinded study of a PF4-dependent assay for HIT diagnosis","volume":"137","author":"Samuelson Bannow","year":"2021","journal-title":"Blood"},{"issue":"9","key":"2025032119474670400_bib20","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1182\/blood.2022017612","article-title":"Cloned antibodies from patients with HIT provide new clues to HIT pathogenesis","volume":"141","author":"Zhu","year":"2023","journal-title":"Blood"},{"issue":"3","key":"2025032119474670400_bib21","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1182\/blood.V72.3.925.bloodjournal723925","article-title":"Heparin-induced thrombocytopenia: laboratory studies","volume":"72","author":"Kelton","year":"1988","journal-title":"Blood"},{"issue":"23","key":"2025032119474670400_bib22","doi-asserted-by":"crossref","first-page":"5021","DOI":"10.1182\/blood-2010-03-276964","article-title":"Monocyte-bound PF4 in the pathogenesis of heparin-induced thrombocytopenia","volume":"116","author":"Rauova","year":"2010","journal-title":"Blood"},{"issue":"1","key":"2025032119474670400_bib23","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1038\/s41467-019-09160-7","article-title":"Neutrophil activation and NETosis are the major drivers of thrombosis in heparin-induced thrombocytopenia","volume":"10","author":"Perdomo","year":"2019","journal-title":"Nat Commun"},{"issue":"10","key":"2025032119474670400_bib24","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1056\/NEJM198703053161004","article-title":"Immune endothelial-cell injury in heparin-associated thrombocytopenia","volume":"316","author":"Cines","year":"1987","journal-title":"N\u00a0Engl J Med"},{"issue":"23","key":"2025032119474670400_bib25","doi-asserted-by":"crossref","first-page":"3651","DOI":"10.1182\/blood-2014-01-549741","article-title":"Spontaneous heparin-induced thrombocytopenia syndrome: 2 new cases and a proposal for defining this disorder","volume":"123","author":"Warkentin","year":"2014","journal-title":"Blood"},{"issue":"6504","key":"2025032119474670400_bib26","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1126\/science.abc5902","article-title":"Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability","volume":"369","author":"Brouwer","year":"2020","journal-title":"Science"},{"issue":"578","key":"2025032119474670400_bib27","doi-asserted-by":"crossref","first-page":"eabd6990","DOI":"10.1126\/scitranslmed.abd6990","article-title":"Stereotypic neutralizing VH antibodies against SARS-CoV-2 spike protein receptor binding domain in patients with COVID-19 and healthy individuals","volume":"13","author":"Kim","year":"2021","journal-title":"Sci Transl Med"},{"issue":"7821","key":"2025032119474670400_bib28","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/s41586-020-2456-9","article-title":"Convergent antibody responses to SARS-CoV-2 in convalescent individuals","volume":"584","author":"Robbiani","year":"2020","journal-title":"Nature"},{"issue":"49","key":"2025032119474670400_bib29","doi-asserted-by":"crossref","first-page":"eabd7114","DOI":"10.1126\/sciimmunol.abd7114","article-title":"Comprehensive mapping of immune perturbations associated with severe COVID-19","volume":"5","author":"Kuri-Cervantes","year":"2020","journal-title":"Sci Immunol"},{"issue":"6","key":"2025032119474670400_bib30","first-page":"1322","article-title":"A\u00a0modified PF4-dependent, CD62p expression assay selectively detects serotonin-releasing antibodies in patients suspected of HIT","volume":"114","author":"Padmanabhan","year":"2015","journal-title":"Thromb Haemostasis"},{"issue":"9","key":"2025032119474670400_bib31","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1182\/blood.2022017612","article-title":"Cloned antibodies from patients with HIT provide new clues to HIT pathogenesis","volume":"141","author":"Zhi","year":"2023","journal-title":"Blood"},{"key":"2025032119474670400_bib32","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.3389\/fimmu.2020.01734","article-title":"Maturation of the human immunoglobulin heavy chain repertoire with age","volume":"11","author":"Ghraichy","year":"2020","journal-title":"Front Immunol"},{"issue":"7744","key":"2025032119474670400_bib33","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/s41586-019-0879-y","article-title":"Commonality despite exceptional diversity in the baseline human antibody repertoire","volume":"566","author":"Briney","year":"2019","journal-title":"Nature"},{"key":"2025032119474670400_bib34","doi-asserted-by":"crossref","first-page":"605170","DOI":"10.3389\/fimmu.2020.605170","article-title":"Deep sequencing of B cell receptor repertoires from COVID-19 patients reveals strong convergent immune signatures","volume":"11","author":"Galson","year":"2020","journal-title":"Front Immunol"},{"issue":"6","key":"2025032119474670400_bib35","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.4049\/jimmunol.1601850","article-title":"Hierarchical clustering can identify B cell clones with high confidence in Ig repertoire sequencing data","volume":"198","author":"Gupta","year":"2017","journal-title":"J Immunol"},{"issue":"7","key":"2025032119474670400_bib36","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/ni.3175","article-title":"Diversity, cellular origin and autoreactivity of antibody-secreting cell population expansions in acute systemic lupus erythematosus","volume":"16","author":"Tipton","year":"2015","journal-title":"Nat Immunol"},{"issue":"20","key":"2025032119474670400_bib37","doi-asserted-by":"crossref","first-page":"3356","DOI":"10.1093\/bioinformatics\/btv359","article-title":"Change-O: a toolkit for analyzing large-scale B cell immunoglobulin repertoire sequencing data","volume":"31","author":"Gupta","year":"2015","journal-title":"Bioinformatics"},{"issue":"3","key":"2025032119474670400_bib38","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.chest.2016.02.641","article-title":"A\u00a0novel PF4-dependent platelet activation assay identifies patients likely to have heparin-induced thrombocytopenia\/thrombosis","volume":"150","author":"Padmanabhan","year":"2016","journal-title":"Chest"},{"issue":"11","key":"2025032119474670400_bib39","first-page":"e138999","article-title":"Neutrophil extracellular traps in COVID-19","volume":"5","author":"Zuo","year":"2020","journal-title":"JCI Insight"},{"issue":"4","key":"2025032119474670400_bib40","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.immuni.2016.04.002","article-title":"Recognition of endogenous nucleic acids by the innate immune system","volume":"44","author":"Roers","year":"2016","journal-title":"Immunity"},{"issue":"73","key":"2025032119474670400_bib41","doi-asserted-by":"crossref","first-page":"73ra19","DOI":"10.1126\/scitranslmed.3001180","article-title":"Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus","volume":"3","author":"Lande","year":"2011","journal-title":"Sci Transl Med"},{"issue":"73","key":"2025032119474670400_bib42","doi-asserted-by":"crossref","first-page":"73ra20","DOI":"10.1126\/scitranslmed.3001201","article-title":"Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus","volume":"3","author":"Garcia-Romo","year":"2011","journal-title":"Sci Transl Med"},{"issue":"1","key":"2025032119474670400_bib43","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1161\/CIRCRESAHA.112.274241","article-title":"Engagement of platelet toll-like receptor 9 by novel endogenous ligands promotes platelet hyperreactivity and thrombosis","volume":"112","author":"Panigrahi","year":"2013","journal-title":"Circ Res"},{"issue":"5","key":"2025032119474670400_bib44","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1084\/jem.20042251","article-title":"Defective B cell tolerance checkpoints in systemic lupus erythematosus","volume":"201","author":"Yurasov","year":"2005","journal-title":"J\u00a0Exp Med"},{"issue":"3","key":"2025032119474670400_bib45","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/nprot.2009.3","article-title":"Rapid generation of fully human monoclonal antibodies specific to a vaccinating antigen","volume":"4","author":"Smith","year":"2009","journal-title":"Nat Protoc"},{"issue":"26","key":"2025032119474670400_bib46","doi-asserted-by":"crossref","first-page":"5209","DOI":"10.1182\/blood-2012-07-445080","article-title":"Platelet secretion is kinetically heterogeneous in an agonist-responsive manner","volume":"120","author":"Jonnalagadda","year":"2012","journal-title":"Blood"},{"issue":"2","key":"2025032119474670400_bib47","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/j.1365-2249.2009.04007.x","article-title":"BAFF: a local and systemic target in autoimmune diseases","volume":"158","author":"Moisini","year":"2009","journal-title":"Clin Exp Immunol"},{"key":"2025032119474670400_bib48","doi-asserted-by":"crossref","first-page":"108556","DOI":"10.1016\/j.clim.2020.108556","article-title":"APRIL expression is upregulated in atopic dermatitis skin lesions and at sites of antigen driven allergic skin inflammation in mice","volume":"219","author":"Leyva-Castillo","year":"2020","journal-title":"Clin Immunol"},{"issue":"2","key":"2025032119474670400_bib49","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1002\/iid3.208","article-title":"Correlation of APRIL with production of inflammatory cytokines during acute malaria in the Brazilian Amazon","volume":"6","author":"Pinna","year":"2018","journal-title":"Immun Inflamm Dis"},{"key":"2025032119474670400_bib50","doi-asserted-by":"crossref","first-page":"997862","DOI":"10.3389\/fimmu.2022.997862","article-title":"CXCL13 is elevated in inflammatory bowel disease in mice and humans and is implicated in disease pathogenesis","volume":"13","author":"Liu","year":"2022","journal-title":"Front Immunol"},{"key":"2025032119474670400_bib51","doi-asserted-by":"crossref","first-page":"767981","DOI":"10.3389\/fimmu.2021.767981","article-title":"SARS-CoV-2 antibodies mediate complement and cellular driven inflammation","volume":"12","author":"Jarlhelt","year":"2021","journal-title":"Front Immunol"},{"issue":"2","key":"2025032119474670400_bib52","doi-asserted-by":"crossref","first-page":"e13275","DOI":"10.1111\/sji.13275","article-title":"Role of Toll-like receptors in the pathogenesis of COVID-19: current and future perspectives","volume":"98","author":"Yang","year":"2023","journal-title":"Scand J Immunol"},{"issue":"5","key":"2025032119474670400_bib53","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1002\/jmv.26826","article-title":"Role of Toll-like receptors in the pathogenesis of COVID-19","volume":"93","author":"Khanmohammadi","year":"2021","journal-title":"J\u00a0Med Virol"},{"issue":"2","key":"2025032119474670400_bib54","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41577-021-00665-1","article-title":"The state of complement in COVID-19","volume":"22","author":"Afzali","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"2025032119474670400_bib55","doi-asserted-by":"crossref","first-page":"6168","DOI":"10.1038\/ncomms7168","article-title":"Toll-like receptor ligands sensitize B-cell receptor signalling by reducing actin-dependent spatial confinement of the receptor","volume":"6","author":"Freeman","year":"2015","journal-title":"Nat Commun"},{"key":"2025032119474670400_bib56","doi-asserted-by":"crossref","first-page":"e46997","DOI":"10.7554\/eLife.46997","article-title":"TLR induces reorganization of the IgM-BCR complex regulating murine B-1 cell responses to infections","volume":"8","author":"Savage","year":"2019","journal-title":"Elife"},{"key":"2025032119474670400_bib57","doi-asserted-by":"crossref","first-page":"775","DOI":"10.3389\/fimmu.2017.00775","article-title":"TLR7\/TLR9- and B cell receptor-signaling crosstalk: promotion of potentially dangerous B cells","volume":"8","author":"Suthers","year":"2017","journal-title":"Front Immunol"},{"issue":"3","key":"2025032119474670400_bib58","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.coi.2005.03.001","article-title":"Regulation of B lymphocyte activation by complement C3 and the B cell coreceptor complex","volume":"17","author":"Rickert","year":"2005","journal-title":"Curr Opin Immunol"},{"issue":"7866","key":"2025032119474670400_bib59","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41586-021-03631-y","article-title":"Diverse functional autoantibodies in patients with COVID-19","volume":"595","author":"Wang","year":"2021","journal-title":"Nature"},{"issue":"1","key":"2025032119474670400_bib60","doi-asserted-by":"crossref","first-page":"5417","DOI":"10.1038\/s41467-021-25509-3","article-title":"New-onset IgG autoantibodies in hospitalized patients with COVID-19","volume":"12","author":"Chang","year":"2021","journal-title":"Nat Commun"},{"issue":"62","key":"2025032119474670400_bib61","doi-asserted-by":"crossref","first-page":"eabl4340","DOI":"10.1126\/sciimmunol.abl4340","article-title":"Autoantibodies neutralizing type I IFNs are present in \u223c4% of uninfected individuals over 70 years old and account for \u223c20% of COVID-19 deaths","volume":"6","author":"Bastard","year":"2021","journal-title":"Sci Immunol"},{"issue":"6515","key":"2025032119474670400_bib62","doi-asserted-by":"crossref","first-page":"eabd4585","DOI":"10.1126\/science.abd4585","article-title":"Autoantibodies against type I IFNs in patients with life-threatening COVID-19","volume":"370","author":"Bastard","year":"2020","journal-title":"Science"},{"issue":"3","key":"2025032119474670400_bib63","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1056\/NEJMc2013656","article-title":"Lupus anticoagulant and abnormal coagulation tests in patients with COVID-19","volume":"383","author":"Bowles","year":"2020","journal-title":"N\u00a0Engl J Med"},{"issue":"17","key":"2025032119474670400_bib64","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.1056\/NEJMc2007575","article-title":"Coagulopathy and antiphospholipid antibodies in patients with COVID-19","volume":"382","author":"Zhang","year":"2020","journal-title":"N\u00a0Engl J Med"},{"issue":"570","key":"2025032119474670400_bib65","doi-asserted-by":"crossref","first-page":"eabd3876","DOI":"10.1126\/scitranslmed.abd3876","article-title":"Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19","volume":"12","author":"Zuo","year":"2020","journal-title":"Sci Transl Med"},{"key":"2025032119474670400_bib66","doi-asserted-by":"crossref","first-page":"587517","DOI":"10.3389\/fimmu.2020.587517","article-title":"Clinical, serological, and histopathological similarities between severe COVID-19 and acute exacerbation of connective tissue disease-associated interstitial lung disease (CTD-ILD)","volume":"11","author":"Gagiannis","year":"2020","journal-title":"Front Immunol"},{"issue":"7934","key":"2025032119474670400_bib67","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/s41586-022-05273-0","article-title":"Dysregulated naive B cells and de novo autoreactivity in severe COVID-19","volume":"611","author":"Woodruff","year":"2022","journal-title":"Nature"},{"issue":"12","key":"2025032119474670400_bib68","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1038\/s41590-020-00814-z","article-title":"Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19","volume":"21","author":"Woodruff","year":"2020","journal-title":"Nat Immunol"},{"issue":"suppl 1","key":"2025032119474670400_bib69","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1182\/blood-2020-138781","article-title":"Polyreactivity and somatic hypermutation analysis reveals the innate B cell origin of human PF4\/heparin reactive antibodies [abstract]","volume":"136","author":"Zhu","year":"2020","journal-title":"Blood"},{"issue":"3","key":"2025032119474670400_bib70","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1046\/j.1365-2567.2001.01159.x","article-title":"Molecular structure of eight human autoreactive monoclonal antibodies","volume":"102","author":"Aguilera","year":"2001","journal-title":"Immunology"},{"issue":"5638","key":"2025032119474670400_bib71","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1126\/science.1086907","article-title":"Predominant autoantibody production by early human B cell precursors","volume":"301","author":"Wardemann","year":"2003","journal-title":"Science"},{"issue":"3","key":"2025032119474670400_bib72","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1084\/jem.180.3.885","article-title":"Analysis of the structural correlates for antibody polyreactivity by multiple reassortments of chimeric human immunoglobulin heavy and light chain V segments","volume":"180","author":"Ichiyoshi","year":"1994","journal-title":"J\u00a0Exp Med"},{"issue":"9","key":"2025032119474670400_bib73","doi-asserted-by":"crossref","first-page":"4526","DOI":"10.4049\/jimmunol.154.9.4526","article-title":"Heavy chain\u00a0variable region, light chain variable region, and heavy chain CDR3 influences on the mono- and polyreactivity and on the affinity of human monoclonal rheumatoid factors","volume":"154","author":"Crouzier","year":"1995","journal-title":"J\u00a0Immunol"},{"key":"2025032119474670400_bib74","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1146\/annurev.iy.12.040194.002415","article-title":"Genetic and structural evidence for antigen selection of anti-DNA antibodies","volume":"12","author":"Radic","year":"1994","journal-title":"Annu Rev Immunol"},{"issue":"7","key":"2025032119474670400_bib75","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1073\/pnas.92.7.2529","article-title":"Human autoantibody recognition of DNA","volume":"92","author":"Barbas","year":"1995","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"2025032119474670400_bib76","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1084\/jem.20031550","article-title":"Surrogate light chain expressing human peripheral B cells produce self-reactive antibodies","volume":"199","author":"Meffre","year":"2004","journal-title":"J\u00a0Exp Med"},{"issue":"8","key":"2025032119474670400_bib77","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1172\/JCI20255","article-title":"Human immunoglobulin selection associated with class switch and possible tolerogenic origins for C delta class-switched B cells","volume":"113","author":"Zheng","year":"2004","journal-title":"J\u00a0Clin Invest"},{"issue":"10","key":"2025032119474670400_bib78","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/s41577-022-00762-9","article-title":"Understanding COVID-19-associated coagulopathy","volume":"22","author":"Conway","year":"2022","journal-title":"Nat Rev Immunol"},{"issue":"8","key":"2025032119474670400_bib79","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1182\/blood.2020010459","article-title":"Another front in COVID-19's perfect storm","volume":"137","author":"Jobe","year":"2021","journal-title":"Blood"},{"issue":"5","key":"2025032119474670400_bib80","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1111\/jth.15283","article-title":"Platelet-activating immune complexes identified in critically ill COVID-19 patients suspected of\u00a0heparin-induced thrombocytopenia","volume":"19","author":"Nazy","year":"2021","journal-title":"J\u00a0Thromb Haemost"},{"issue":"5","key":"2025032119474670400_bib81","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1111\/jth.15262","article-title":"COVID-19 patients often show high-titer non-platelet-activating anti-PF4\/heparin IgG antibodies","volume":"19","author":"Brodard","year":"2021","journal-title":"J\u00a0Thromb Haemost"},{"issue":"6","key":"2025032119474670400_bib82","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1002\/rth2.12416","article-title":"The challenges of diagnosing heparin-induced thrombocytopenia in patients with COVID-19","volume":"4","author":"May","year":"2020","journal-title":"Res Pract Thromb Haemost"},{"issue":"10","key":"2025032119474670400_bib83","doi-asserted-by":"crossref","first-page":"E295","DOI":"10.1002\/ajh.25935","article-title":"Heparin induced thrombocytopenia antibodies in COVID-19","volume":"95","author":"Patell","year":"2020","journal-title":"Am J Hematol"},{"issue":"19","key":"2025032119474670400_bib84","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1161\/CIRCULATIONAHA.120.049015","article-title":"Heparin-induced thrombocytopenia in severe COVID-19","volume":"142","author":"Daviet","year":"2020","journal-title":"Circulation"},{"issue":"47","key":"2025032119474670400_bib85","doi-asserted-by":"crossref","first-page":"e2213361119","DOI":"10.1073\/pnas.2213361119","article-title":"Anti-PF4 antibodies associated with disease severity in COVID-19","volume":"119","author":"Liu","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"2025032119474670400_bib86","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1080\/09537104.2022.2042238","article-title":"Anti-PF4\/polyanion antibodies in COVID-19 patients are associated with disease severity and pulmonary pathology","volume":"33","author":"Ueland","year":"2022","journal-title":"Platelets"},{"issue":"3","key":"2025032119474670400_bib87","first-page":"e11","article-title":"Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination","volume":"385","author":"Eichinger","year":"2021","journal-title":"N\u00a0Engl J Med"},{"issue":"22","key":"2025032119474670400_bib88","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1056\/NEJMoa2104882","article-title":"Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination","volume":"384","author":"Schultz","year":"2021","journal-title":"N\u00a0Engl J Med"},{"issue":"20","key":"2025032119474670400_bib89","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1056\/NEJMc2105869","article-title":"Thrombotic thrombocytopenia after Ad26.COV2.S vaccination","volume":"384","author":"Muir","year":"2021","journal-title":"N\u00a0Engl J Med"},{"issue":"1","key":"2025032119474670400_bib90","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1182\/blood.2021014588","article-title":"Monoclonal and oligoclonal anti-platelet factor 4 antibodies mediate VITT","volume":"140","author":"Kanack","year":"2022","journal-title":"Blood"},{"issue":"15","key":"2025032119474670400_bib91","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1182\/blood.2022016474","article-title":"Vaccine-induced immune thrombotic thrombocytopenia is mediated by a stereotyped clonotypic antibody","volume":"140","author":"Wang","year":"2022","journal-title":"Blood"},{"issue":"7873","key":"2025032119474670400_bib92","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41586-021-03744-4","article-title":"Antibody epitopes in vaccine-induced immune thrombotic thrombocytopaenia","volume":"596","author":"Huynh","year":"2021","journal-title":"Nature"},{"issue":"14","key":"2025032119474670400_bib93","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1182\/blood.2021012938","article-title":"Anti-platelet factor 4 antibodies causing VITT\u00a0do not cross-react with SARS-CoV-2 spike protein","volume":"138","author":"Greinacher","year":"2021","journal-title":"Blood"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/145\/6\/635\/2360986\/blood_bld-2024-025010-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/145\/6\/635\/2360986\/blood_bld-2024-025010-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T21:05:49Z","timestamp":1742591149000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/145\/6\/635\/526138\/Prothrombotic-antibodies-targeting-the-spike"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,6]]},"references-count":93,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,2,6]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2024025010","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,6]]}}}