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bioRxiv · 10.1101/2025.04.22.646545

Transcription-based identification of uncharacterized genes in the human immune response

Vorsteveld, E. E.·Kersten, S.·Kaffa, C.·Simons, A.·'t Hoen, P. A. C.·Netea, M. G.·Hoischen, A.
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Abstract

Host-pathogen interactions are shaped by the nature of the pathogen and by host-related factors. The human host responses can be characterized in microbe-stimulated immune cells using transcriptomics. We set out to characterize gene expression changes as a result of microbial in vitro stimulation in RPMI-cultured human primary immune cells, using four pathogen ligands representing bacteria (LPS and S. aureus), viruses (Poly(I:C)) and fungi (C. albicans) for 4 and 24 hours, resulting in a total of 52 samples for analysis. We analyze the transcriptional changes on gene- and pathway level, highlighting common and distinct effects of pathogen stimulation. We highlight genes without a known function that were differentially expressed as a common effect of pathogen stimulation. We find uncharacterized genes such as KIAA0040 and CYRIA to be co-expressed with genes involved in innate immunity and downstream signaling from the PRRs, respectively. We identify 901 variants in uncharacterized genes in a cohort of patients with rare immune disorders, prioritizing 5 candidate variants in 4 genes that could underly these diseases. Our results therefore indicate the potential role of these genes the human immune response and provides candidate variants with potential relevance in rare immune-mediated diseases.

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Vorsteveld, E. E., Kersten, S., Kaffa, C., Simons, A., 't Hoen, P. A. C., Netea, M. G., Hoischen, A.. 2025-04-24. Transcription-based identification of uncharacterized genes in the human immune response. https://doi.org/10.1101/2025.04.22.646545

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