{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T20:08:19Z","timestamp":1778875699482,"version":"3.51.4"},"reference-count":73,"publisher":"American Society for Clinical Investigation","issue":"8","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":55,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["NIH HL148120 (RW)"],"award-info":[{"award-number":["NIH HL148120 (RW)"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["NIH HL161127 (RW)"],"award-info":[{"award-number":["NIH HL161127 (RW)"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["NIH HL167668 (RW,DW)"],"award-info":[{"award-number":["NIH HL167668 (RW,DW)"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["NIH HL130724 (DW)"],"award-info":[{"award-number":["NIH HL130724 (DW)"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["NIH AI079087 (DW)"],"award-info":[{"award-number":["NIH AI079087 (DW)"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["AHA 25PRE1374068 (LZ)"],"award-info":[{"award-number":["AHA 25PRE1374068 (LZ)"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["AHA 20PRE35210461 (WZ)"],"award-info":[{"award-number":["AHA 20PRE35210461 (WZ)"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,22]]},"abstract":"<jats:p>\n                    Patients with COVID-19 who develop platelet-activating antibodies represent a subset at heightened thrombotic risk, yet the immune features associated with this response remains to be defined. We applied single-cell RNA-seq of B and T cells, single B cell V(D)J-seq, and plasma cytokine and chemokine analysis to define immune signatures distinguishing patients who did (PEA\n                    <jats:sup>+<\/jats:sup>\n                    ) or did not (PEA\n                    <jats:sup>\u2013<\/jats:sup>\n                    ) develop these antibodies. Patients positive for PEA showed prominent transcriptional enrichment of inflammatory, antigen presentation, and B cell receptor signaling pathways within antigen-experienced B cell subsets. Expanded B cell clones in patients positive for PEA were disproportionately enriched within atypical memory B cells and exhibited upregulated IFN-\u03b3\u2013response signatures, increased proliferative mutational patterns, limited class switching, and a significant overrepresentation of RKH\/Y5 heavy-chain motifs associated with platelet-activating antibodies, consistent with an extrafollicular-biased response. Parallel T cell profiling revealed IL-12 pathway enrichment across most T cell subsets, increased IFN-\u03b3 transcription, and elevated plasma levels of Th1-associated cytokines in patients positive for PEA. Collectively, these data highlight a coordinated inflammatory environment marked by Th1-skewed T cell activation and selective expansion of atypical memory B cell clones carrying RKH\/Y5 motifs, defining immunologic features associated with platelet-activating antibody development in COVID-19.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.201033","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T18:00:45Z","timestamp":1776794445000},"source":"Crossref","is-referenced-by-count":0,"title":["Atypical memory B cell clonal expansion and inflammatory programs associate with platelet-activating antibody development in COVID-19"],"prefix":"10.1172","volume":"11","author":[{"given":"Nathan","family":"Witman","sequence":"first","affiliation":[{"name":"Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA."},{"name":"Versiti Blood Research Institute, Milwaukee, Wisconsin, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Yu","sequence":"additional","affiliation":[{"name":"Versiti Blood Research Institute, Milwaukee, Wisconsin, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Northwestern University, Chicago, Illinois, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kexin","family":"Gai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Northwestern University, Chicago, Illinois, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhong","family":"Chen","sequence":"additional","affiliation":[{"name":"Versiti Blood Research Institute, Milwaukee, Wisconsin, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA."},{"name":"Versiti Blood Research Institute, Milwaukee, Wisconsin, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA."},{"name":"Versiti Blood Research Institute, Milwaukee, Wisconsin, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA."},{"name":"Versiti Blood Research Institute, Milwaukee, Wisconsin, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongwei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Versiti Blood Research Institute, Milwaukee, Wisconsin, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shawn","family":"Jobe","sequence":"additional","affiliation":[{"name":"Versiti Blood Research Institute, Milwaukee, Wisconsin, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary Beth","family":"Graham","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1562-9218","authenticated-orcid":true,"given":"Weiguo","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA."},{"name":"Versiti Blood Research Institute, Milwaukee, Wisconsin, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Demin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA."},{"name":"Versiti Blood Research Institute, Milwaukee, Wisconsin, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renren","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA."},{"name":"Versiti Blood Research Institute, Milwaukee, Wisconsin, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"232","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-020-00469-1"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00762-9"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.86002"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2024015076"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024025010"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2213361119"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s11239-025-03116-z"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2020.08.017"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-11-709873"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-00814-z"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05273-0"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-092419-031130"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108684"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.31138\/mjr.31.3.311"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05736-y"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1241474"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.025"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abg5021"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc8511"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.09.002"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-01858-1"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.11.006"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abg8384"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.05.001"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0378-1"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03750-7"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.12.063"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09097-1"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311586"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb0457"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2008.08.005"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.552295"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-024-02814-x"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102057"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2782"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2015.09.006"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.41641"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202250319"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.01.002"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1018571108"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e3182841263"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12741"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.1.315"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200009)30:9<2604::AID-IMMU2604>3.0.CO;2-6"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1126\/science.8016643"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1997.tb03921.x"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201141762"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022017612"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.10.069"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/nri1001"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.092141999"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2011.06.001"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.07.040189.001045"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074900"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.07218"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.108496"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.06.013"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02378-14"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-012-8268-8"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aax0904"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.08.015"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1007\/s40744-022-00513-1"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-015-0324-5"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000003358"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0654-x"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-024-01020-z"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1113"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2015.12.004"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv359"},{"issue":"suppla 1","key":"B72","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","volume":"136","author":"Zhu","year":"2020","journal-title":"Blood"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks457"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/201033\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T19:14:27Z","timestamp":1778872467000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/201033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,26]]},"references-count":73,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,2,26]]},"published-print":{"date-parts":[[2026,4,22]]}},"alternative-id":["10.1172\/jci.insight.201033"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.201033","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,26]]},"article-number":"e201033"}}