First study to show gene expression changes in divers with ‘the bends’ reveals key role of genes for inflammation and immunity
Diving and hyperbaric medicine are relatively young and rapidly evolving specialties. Several pathologies dealt with regularly in this discipline remain incompletely understood.
Decompression sickness (DCS) is a potentially fatal condition usually observed after scuba diving. It involves bubble formation in blood and tissues from dissolved inert gas secondary to decreases in ambient pressure (decompression). Its manifestations range from a mild illness to a rapidly life-threatening one. The standard treatment for DCS involves oxygen delivered at an elevated ambient pressure – hyperbaric oxygen (HBO).
To date, limited gene expression studies in humans have focused on cohorts of divers completing uneventful freediving or scuba diving, and showed that diving is a powerful physiologic stressor that affects the expression of several genes.
A team of researchers from the Faculty of Medicine and Surgery and Centre of Molecular Medicine and Biobanking, in collaboration with Norwegian University for Science and Technology, Trondheim and the Diving and Hyperbaric unit, Mater Dei Hospital have performed the first RNA-sequencing study of human DCS.
This research has shown that DCS induces the enrichment of transcripts involved in inflammation, activation of the innate and adaptive immune system as well as a shift in white blood cell subtypes that was reversed in response to HBO. The observed changes highlight a continuum between the responses elicited by uneventful diving and diving complicated by DCS. This research has provided the first genomic signature of DCS and will help secure Malta’s current reputation of being an excellent centre for hyperbaric medicine.
“We showed that decompression sickness activates genes involved in white blood cell activity, inflammation and the generation of inflammatory proteins called cytokines,” explained Dr Nikolai Pace of the University of Malta, a researcher involved in the study. “Basically, decompression sickness activates some of the most primitive body defense mechanisms that are carried out by certain white blood cells.”
Interestingly, these genetic changes had diminished in samples taken at 48 hours after the dive, after the patients had been treated with hyperbaric oxygen therapy. The findings provide a first step towards potentially developing a diagnostic test for decompression sickness, and may also reveal new treatment targets.
(A) PCA analysis of gene expression across sequenced libraries repeated for DCS cases at T1 and T2 and uneventful diving controls at T1 and T2. PC1 and PC2 define 40 and 12% of the observed variance. A third component, PC3, defines 8% of the variance (not shown). Importantly, two distinct but broad clusters can be detected, largely defined by DCS cases at T1 and most of the controls in aggregate. (B) Heat map showing the top 200 DEGs across the four biological groups in this study. Genes on heatmap are organized by hierarchical clustering based on the overall similarity in expression patterns. Upregulated genes are shown in shades of red while downregulated genes are shown in shades of blue.
“We hope that our findings can aid the development of a blood-based biomarker test for human decompression sickness that can facilitate diagnosis or monitoring of treatment response,” said Prof Ingrid Eftedal of the Norwegian University of Science and Technology, who was also involved in the project. “This will require further evaluation and replication in larger groups of patients.”
Source – University of Malta