Molecular analysis of immune cell subsets and cytokine profiles in septic Vietnamese patients

Sepsis remains a Major global health burden, accounting for an estimated 11 million deaths annually, and is characterized by a profoundly dysregulated host immune response to infection. Despite its significant morbidity and mortality, the immunopathogenesis of sepsis-particularly within underrepresented populations-remains inadequately understood. Here we report distinct immunological signatures associated with clinical outcomes among Vietnamese septic patients. To our knowledge, this represents the first comprehensive investigation of both cellular and cytokine immune parameters in the sepsis population. Our findings demonstrate that survivors of sepsis exhibited a higher proportion of circulating B cells, whereas non-survivors showed increased activation of T and natural killer (NK) cells, marked by elevated expression of activation molecules such as CD69 and GITR. There was a notable reduction in B cell numbers, and further phenotypic analysis revealed signs of B cell exhaustion, indicated by increased CD21low expression, as well as depletion of both memory and naïve B cell subsets. Collectively, these results establish compromised humoral immunity in septic patients. T cells in septic patients displayed a skewing toward effector memory phenotypes, and NK cells demonstrated impaired cytotoxic potential, as evidenced by decreased expression of key the key activating receptors including NKG2D and DNAM-1. Concurrent cytokine profiling revealed significantly elevated concentrations of both pro- and anti-inflammatory mediators in septic patients. A significantly diminished percentage of CD8⁺CD45RA⁺CD197⁻ T cells, alongside markedly elevated interleukin-6 (IL-6) levels, was observed in non-survivors, strongly supporting their role as key prognostic biomarkers for predicting sepsis-related mortality. Interestingly, tumor necrosis factor-alpha (TNF-α) levels did not significantly differ between those who survived and those who did not, a result that diverges from some prior reports and highlights the possibility of population-specific immunological nuances.