Type I interferon signature strength correlates with alloimmunization-associated transcriptomic programs in systemic lupus erythematosus: A multi-cohort analysis
- 1Department of Laboratory Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon, South Korea
Abstract
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.
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BibTeX
@article{yoo2026type,
title = {{Type I interferon signature strength correlates with alloimmunization-associated transcriptomic programs in systemic lupus erythematosus: A multi-cohort analysis}},
author = {Jaeeun Yoo},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0347443},
url = {https://doi.org/10.1371/journal.pone.0347443},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Type I interferon signature strength correlates with alloimmunization-associated transcriptomic programs in systemic lupus erythematosus: A multi-cohort analysis
AU - Jaeeun Yoo
PY - 2026
DA - 2026/09/15
JO - PLOS One
DO - 10.1371/journal.pone.0347443
UR - https://doi.org/10.1371/journal.pone.0347443
AB - 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.
SN - 1932-6203
ER -