2026-10-14T14:56:17Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33815013 2026-09-15T18:03:24Z category_12 category_13 category_39 category_46 category_734 category_61 category_122 category_132 portal_5 item_type_3 month_year_09_2026

<p>Baseline cohort characteristics.</p> Jaeeun Yoo (4720956) Cell Biology Genetics Ecology Immunology Biological Sciences not elsewhere classified Developmental Biology Mental Health Infectious Diseases systemic lupus erythematosus replication &# 8211 provide translational rationale prone transcriptomic landscape computed per sample clinically significant complication associated transcriptomic programs associated immune programs findings identify ifn findings suggest whole blood validation design three cohorts spearman correlation significantly elevated seq cohorts pathway activity murine models differential expression candidate biomarker <div><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 = 150 SLE) in a pre-specified discovery–replication–validation 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 < 0.01 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 (ρ = +0.77, + 0.51, + 0.60; all FDR q < 0.05); 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.</p></div> 2026-09-15T18:03:13Z Dataset Dataset 10.1371/journal.pone.0347443.t001 https://figshare.com/articles/dataset/_p_Baseline_cohort_characteristics_p_/33815013 CC BY 4.0