Functional screening assay as biomarker for course of sepsis

Sepsis, a life-threatening organ dysfunction caused by a dysregulated host immune response to infection, is a major health problem with high incidence and mortality. It has been shown that hyperinflammation and immunosuppression play a crucial role in the different stages of sepsis. Biomarkers could be helpful for categorizing patients based on their individual immune status, enabling diagnosis, prognosis, and effective treatments for sepsis to restore immune system homeostasis.

Our aim was to investigate different functional immune assays to identify potential biomarkers for the clinical course of sepsis. In a translational observation study, the patients were stratified according to severity of sepsis (Sequential Organ Failure Assessment (SOFA) Score) including existence of a septic shock or multi-organ failure and blood was drawn on day 0, 3 and 7. Healthy blood donors were used as controls. PBMCs were isolated from peripheral blood, subsequently frozen, and then thawed for analysis. In addition to measurement of cell proliferation, expression of T and B cell surface markers and cytokine production, demographic data, clinical and laboratory parameters as well as concomitant medication were also collected.

The study cohort consisted of mixed genders with an average age of 58.6 (standard deviation, SD: ± 22) years. Mean SOFA-Score at baseline was 5.6 (± 1.8). Preliminary data showed reduction of the expression of T cell activation markers CD25 and CD71 and the B cell activation marker CD86 in patients with sepsis compared to healthy controls with a further reduction of T cell markers during the course of sepsis. Additionally, in septic patients compared to healthy controls, pro-inflammatory cytokines such as TNF-α, IL-1β and IFN-γ were downregulated, whereas anti-inflammatory cytokines such as IL-10 were increased.

Results indicate significant fluctuations in the immune response in different phases of sepsis compared to healthy controls. However, further studies are needed to elucidate the underlying mechanisms and accurately monitor the immune response. Different biomarkers need to be explored and rigorously assessed to ensure reliable reflections of the patient"s clinical status, providing utility in terms of patient stratification, prognosis and the development of new treatment options.

No conflicts of interest.