# Gene expression profiling identifies potential biomarkers for vaso-occlusive episodes in sickle cell disease

## TL;DR

This study identifies genes and biological pathways involved in pain episodes in sickle cell disease, offering potential biomarkers for diagnosis and treatment.

## Contribution

The study discovers four genes elevated during vaso-occlusive episodes and highlights differences in immune and erythroid cell pathways in SCD patients.

## Key findings

- Genes FAM20A, IL1B, MS4A4A, and SERPINB2 are elevated during vaso-occlusive episodes in most patients.
- CD45+ cells show enriched pathways in complement activation, coagulation, and IL-6/JAK/STAT3 signaling during episodes.
- Chronic pain patients show 44% higher pathway enrichment during vaso-occlusive episodes compared to non-chronic pain patients.

## Abstract

Vaso-occlusive episodes (VOEs) or acute pain events, involving complex interactions between sickle erythrocytes and other blood cells, are a hallmark of sickle cell disease (SCD). In this study, we analyzed changes in peripheral blood transcriptomes between steady state and VOEs 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 (VOEs). We performed RNA-Seq profiling of CD45+ leukocytes and CD71+ erythroid cells. Pathways linked to complement activation, coagulation, and IL-6/JAK/STAT3 signaling were enriched during VOEs 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 during VOEs. We then analyzed the expression changes of genes in patients with longitudinal data to determine potential biomarkers for VOEs. Expression of 4 genes — FAM20A, IL1B, MS4A4A, and SERPINB2 — was elevated during VOEs compared with steady state in the majority of patients. Furthermore, our results indicate that patients experiencing chronic pain exhibited 44% increased enrichment of significant pathways during VOEs when compared with patients without chronic pain.

RNA-Seq profiling of immune and erythroid cells from SCD patients shows multiple genes and biological pathways altered during vaso-occlusive episodes in sickle cell disease