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Data · dataset · 2026

Table 2_Transcriptomic evidence of an IFN-gamma-associated inflammatory state in active visceral leishmaniasis: an exploratory comparison with pediatric HLH.xlsx

Listed in Deakin Research Online

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Background<p>Visceral leishmaniasis (VL) can progress to secondary hemophagocytic lymphohistiocytosis (HLH), but transcriptomic similarities between active VL and pediatric HLH remain uncertain.</p>Methods<p>We integrated VL whole-blood expression data (GSE125992), sorted CD68-positive monocyte bulk-expression data from pediatric HLH and severe sepsis (GSE150707), and supportive Leishmania-infected mouse spleen single-cell data (GSE240385).

Differential expression, pathway enrichment, an exploratory 132-gene HLH-versus-sepsis-derived ssGSEA score, FARDEEP-LM22 deconvolution, signature-excluded WGCNA, CellChat, and a refitted three-gene classifier were evaluated.</p>Results<p>Active VL showed IFN-gamma-associated expression changes, including higher CXCL9 and CXCL10. The exploratory 132-gene score was higher in ActiveCase than EHC samples (Mann-Whitney P = 0.000637).

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Across 22 deconvolved cell types, only M1 macrophages showed an FDR-supported positive correlation with this score (rho = 0.787, BH q = 0.000503). After all 132 score genes were excluded before network construction, a 124-gene magenta module remained associated with the score (rho = 0.837, BH q = 4.29 × 10^-5). A refitted IFNG/GBP5/MX2 classifier achieved a same-study validation AUC of 0.917 (bootstrap 95% CI 0.733-1.000), but the validation set contained only 16 samples.</p>Conclusion<p>These public datasets support an IFN-gamma-associated inflammatory state in active VL and exploratory cross-compartment convergence with pediatric HLH.

The 132-gene score, deconvolution, network, and classifier results are hypothesis-generating and do not establish HLH specificity, cellular causality, independent external validity, or clinical HLH prediction.</p>

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