Blood from septic patients with necrotising soft tissue infection treated with hyperbaric oxygen reveal different gene expression patterns compared to standard treatment.

Abstract

Background: Sepsis and shock are common complications of necrotising soft tissue infections (NSTI). Sepsis encompasses different endotypes that are associated with specific immune responses. Hyperbaric oxygen (HBO₂) treatment activates the cells oxygen sensing mechanisms that are interlinked with inflammatory pathways. We aimed to identify gene expression patterns associated with effects of HBO₂ treatment in patients with sepsis caused by NSTI, and to explore sepsis-NSTI profiles that are more receptive to HBO₂ treatment.

Methods: An observational cohort study examining 83 NSTI patients treated with HBO₂ in the acute phase of NSTI, fourteen of whom had received two sessions of HBO₂ (HBOx2 group), and another ten patients (non-HBO group) who had not been exposed to HBO₂. Whole blood RNA sequencing and clinical data were collected at baseline and after the intervention, and at equivalent time points in the non-HBO group. Gene expression profiles were analysed using machine learning techniques to identify sepsis endotypes, treatment response endotypes and clinically relevant transcriptomic signatures of response to treatment.

Results: We identified differences in gene expression profiles at follow-up between HBO₂-treated patients and patients not treated with HBO₂. Moreover, we identified two patient endotypes before and after treatment that represented an immuno-suppressive and an immune-adaptive endotype respectively, and we characterized the genetic profile of the patients that transition from the immuno-suppressive to the immune-adaptive endotype after treatment. We discovered one gene MTCO2P12 that distinguished individuals who altered their endotype in response to treatment from non-responders.

Conclusion: The global gene expression pattern in blood changed in response to HBO₂ treatment in a direction associated with clinical biochemistry improvement, and the study provides potential novel biomarkers and pathways for monitoring HBO₂ treatment effects and predicting an HBO₂ responsive NSTI-sepsis profile.

Trial registration: Biological material was collected during the INFECT study, registered at ClinicalTrials.gov (NCT01790698) 04/02/2013.