{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T03:03:52Z","timestamp":1763348632115,"version":"3.44.0"},"reference-count":14,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"unspecified","delay-in-days":30,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR075134","AR077266","AR081654","T32 AR007108"],"award-info":[{"award-number":["AR075134","AR077266","AR081654","T32 AR007108"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Lupus Sci Med"],"accepted":{"date-parts":[[2024,1,22]]},"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To illuminate the poorly understood aetiology of SLE by comparing the gene expression profile of SLE neutrophils with that of neutrophils from patients infected by SARS-CoV-2, a disease (COVID-19) with well-defined antigens and a similar type I interferon response.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>RNA sequencing of neutrophils from patients with SLE (n=15) and healthy controls (n=12) was analysed for differential gene expression and modulated pathways. The same analyses were performed on a similar neutrophil dataset from patients with SARS-CoV-2 infection (n=30) and healthy controls (n=8). Next, we carried out comparative analyses to identify common and unique transcriptional changes between the two disease contexts, emphasising genes regulated in opposite directions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified 372 differentially expressed genes in SLE neutrophils compared with healthy donor neutrophils (\u22652\u2009fold, p&lt;0.05), 181 of which were concordant with transcriptional changes in SARS-CoV-2-infected individuals compared with their respective healthy controls. In contrast, 118 genes demonstrated statistically significant alterations exclusive to SLE, including 28 genes that were differentially expressed in opposite directions in the two diseases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The substantial overlap between neutrophil responses in SLE and COVID-19 suggests that the unknown cause of SLE is functionally similar to a viral infection and drives a similar immune activation and type I interferon response. Conversely, the genes regulated in the opposite direction represent responses unique to SLE. These include tyrosylprotein sulfotransferase-1 and nucleic acid deaminases of the APOBEC family, which can catalyse cytosine-to-uridine editing of both RNA and DNA, and other RNA-modifying enzymes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/lupus-2023-001059","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T23:10:12Z","timestamp":1706742612000},"page":"e001059","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Large overlap in neutrophil transcriptome between lupus and COVID-19 with limited lupus-specific gene expression"],"prefix":"10.1136","volume":"11","author":[{"given":"Rayan","family":"Najjar","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noga","family":"Rogel","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose Mario Bello","family":"Pineda","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison","family":"Bays","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5912-8840","authenticated-orcid":false,"given":"Tomas","family":"Mustelin","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"2025091512303355000_11.1.e001059.1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902199"},{"key":"2025091512303355000_11.1.e001059.2","doi-asserted-by":"crossref","unstructured":"Skopelja-Gardner S , Tai J , Sun X , et al . Acute skin exposure to ultraviolet light triggers neutrophil-mediated kidney inflammation. Proc Natl Acad Sci U S A 2021;118. doi:10.1073\/pnas.2019097118","DOI":"10.1073\/pnas.2019097118"},{"key":"2025091512303355000_11.1.e001059.3","doi-asserted-by":"crossref","DOI":"10.1186\/s13100-023-00293-7","article-title":"Expression of L1 retrotransposons in granulocytes from patients with active systemic lupus erythematosus","volume":"14","author":"Ukadike","year":"2023","journal-title":"Mob DNA"},{"key":"2025091512303355000_11.1.e001059.4","doi-asserted-by":"crossref","first-page":"100779","DOI":"10.1016\/j.xcrm.2022.100779","article-title":"Longitudinal characterization of circulating neutrophils uncovers phenotypes associated with severity in hospitalized COVID-19 patients","volume":"3","author":"LaSalle","year":"2022","journal-title":"Cell Rep Med"},{"key":"2025091512303355000_11.1.e001059.5","doi-asserted-by":"crossref","DOI":"10.1186\/s13073-020-00823-5","article-title":"Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients","volume":"13","author":"Aschenbrenner","year":"2021","journal-title":"Genome Med"},{"key":"2025091512303355000_11.1.e001059.6","doi-asserted-by":"crossref","first-page":"109660","DOI":"10.1016\/j.clim.2023.109660","article-title":"Molecular characterization of PANoptosis-related genes with features of immune dysregulation in systemic lupus erythematosus","volume":"253","author":"Sun","year":"2023","journal-title":"Clin Immunol"},{"key":"2025091512303355000_11.1.e001059.7","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s42003-021-01829-4","article-title":"IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection","volume":"4","author":"Rosa","year":"2021","journal-title":"Commun Biol"},{"key":"2025091512303355000_11.1.e001059.8","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-87024-1","article-title":"Sustained high expression of multiple APOBEC3 cytidine deaminases in systemic lupus erythematosus","volume":"11","author":"Perez-Bercoff","year":"2021","journal-title":"Sci Rep"},{"key":"2025091512303355000_11.1.e001059.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.03.036"},{"key":"2025091512303355000_11.1.e001059.10","doi-asserted-by":"publisher","DOI":"10.1038\/nature03238"},{"key":"2025091512303355000_11.1.e001059.11","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkj416"},{"key":"2025091512303355000_11.1.e001059.12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603313103"},{"key":"2025091512303355000_11.1.e001059.13","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20191766","article-title":"Antibodies against human endogenous retrovirus K102 envelope activate neutrophils in systemic lupus erythematosus","volume":"218","author":"Tokuyama","year":"2021","journal-title":"J Exp Med"},{"key":"2025091512303355000_11.1.e001059.14","first-page":"1306","article-title":"Autoantibodies against the envelope proteins of endogenous retroviruses K102 and K108 in patients with systemic lupus erythematosus correlate with active disease","volume":"40","author":"Khadjinova","year":"2022","journal-title":"Clin Exp Rheumatol"}],"container-title":["Lupus Science &amp; Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/lupus-2023-001059","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T19:30:40Z","timestamp":1757964640000},"score":1,"resource":{"primary":{"URL":"https:\/\/lupus.bmj.com\/lookup\/doi\/10.1136\/lupus-2023-001059"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":14,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1,31]]},"published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1136\/lupus-2023-001059"],"URL":"https:\/\/doi.org\/10.1136\/lupus-2023-001059","relation":{},"ISSN":["2053-8790"],"issn-type":[{"type":"electronic","value":"2053-8790"}],"subject":[],"published":{"date-parts":[[2024,1]]}}}