Gene Expression Profiling Identifies Potential Biomarkers for Vaso-Occlusive Episodes in Sickle Cell Disease

Vaso-occlusive episodes (VOE) or acute pain events, involving complex interactions between sickle erythrocytes and other blood cells, are a hallmark symptom of sickle cell disease (SCD). In this study, we analyzed changes in peripheral blood transcriptomes between steady state and VOE in individuals with SCD. We followed a cohort of 174 individuals with SCD with or without chronic pain and collected peripheral blood at clinic visits (steady state) and during hospitalizations (VOE). We performed RNA-Seq profiling of CD45+ leukocytes and CD71+ erythroid cells. Pathways linked to complement activation, coagulation, and IL6-JAK-STAT3 signaling were enriched at VOE in the CD45+ cells. Contrastingly, the CD71+ cells showed an enrichment of pathways related to the cell cycle such as mTORC1 signaling and the G2M checkpoint. Expression of four genes—FAM20A, IL1B, MS4A4A, and SERPINB2—were elevated during VOE compared to steady state in a majority of patients.