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Whole-blood transcriptional signatures composed of erythropoietic and Nrf2-regulated genes differ between cerebral malaria and severe malarial anemia

ABSTRACT: We compared genome-wide transcription profiles of whole blood obtained from Ugandan children with acute CM (n=17) or SMA (n=17) and community children without Plasmodium falciparum infection (n=12) and determined the relationships between gene expression, hematological indices, and relevant plasma biomarkers. Results demonstrated both CM and SMA predominantly upregulated enrichment of dendritic cell (DC), inflammatory/TLR/chemokines, monocyte, and antigen presentation modules but downregulated enrichment of lymphocyte modules. Neurodegenerative disease pathways showed modest upregulation during CM. Nrf2-regulated genes were over-expressed in children with SMA compared to CM, especially those with HbSS, corresponding with increased plasma heme oxygenase-1. Reticulocyte-specific gene expression was markedly decreased in CM relative to SMA despite higher hemoglobin levels and appropriate increases in erythropoietin. Viral sensing/IRF2 module expression and plasma IP-10/CXCL10 negatively correlated with reticulocyte-specific signatures. This study concludes that, compared to SMA, CM is associated with downregulation of Nrf2-related and reticulocyte-specific signatures by whole-blood transcriptomics. Future studies are needed to confirm these findings and assess pathways that may be amenable to interventions to ameliorate CM and SMA.

ORGANISM(S): Homo sapiens

PROVIDER: GSE117613 | GEO | 2018/07/28

REPOSITORIES: GEO

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