{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T19:02:19Z","timestamp":1789498939259,"version":"build-2803163510"},"reference-count":19,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Red blood cell (RBC) alloimmunization is a clinically significant complication in transfused patients whose immunological determinants remain incompletely understood. Type I interferon (IFN-I) signaling drives RBC alloimmunization in murine models, and systemic lupus erythematosus (SLE) is characterized by constitutive IFN-I hyperactivation alongside elevated alloimmunization rates. We analyzed three publicly available SLE RNA-seq cohorts (GSE72509, GSE112087, GSE122459; whole blood and PBMC; total n\u2009=\u2009150 SLE) in a pre-specified discovery\u2013replication\u2013validation design. A 14-gene IFN-I signature score was computed per sample; differential expression, gene set enrichment analysis, and Spearman correlation were performed independently per cohort. IFN-I scores were significantly elevated in SLE versus healthy controls in all three cohorts (p\u2009&lt;\u20090.01 each). IFN-high SLE patients showed 665 differentially expressed genes, with enrichment of alloimmunization-associated and plasmablast differentiation gene sets confirmed by GSEA. The alloimmunization signature score correlated significantly with IFN-I score across all three independent cohorts (\u03c1\u2009=\u2009+0.77,\u2009+\u20090.51,\u2009+\u20090.60; all FDR q\u2009&lt;\u20090.05); Tfh differentiation showed no association in any cohort. These findings suggest that IFN-I pathway activity in SLE is associated with an alloimmunization-prone transcriptomic landscape, To our knowledge, this represents the first human transcriptomic evidence that IFN-I pathway activity in SLE is coupled to alloimmunization-associated immune programs in vivo. These findings identify IFN-I score as a candidate biomarker of alloimmunization susceptibility in SLE and provide translational rationale for prospective studies incorporating transfusion outcome data.<\/jats:p>","DOI":"10.1371\/journal.pone.0347443","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:02:57Z","timestamp":1789495377000},"page":"e0347443","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Type I interferon signature strength correlates with alloimmunization-associated transcriptomic programs in systemic lupus erythematosus: A multi-cohort analysis"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9917-5393","authenticated-orcid":true,"given":"Jaeeun","family":"Yoo","sequence":"first","affiliation":[{"name":"The Catholic University of Korea","place":["Incheon, South Korea"],"department":["Department of Laboratory 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