The Presence of PDL-1 on CD8+ Lymphocytes Is Linked to Survival in Neonatal Sepsis

Abstract

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Neonatal sepsis is the main cause of death in newborns, especially preterm infants. The pathogenesis of sepsis is based on a hyper-inflammatory syndrome combined with an immunosuppressive mechanism in sepsis. This study aimed to find critical parameters that are associated with the outcome of newborns with suspected sepsis. Understanding the association might have clinical relevance for immuno-monitoring, outcome prediction, and targeted therapy. Methods: A total of 210 newborn infants no older than 4 days with suspected sepsis at admission in Karaganda (Kazakhstan) were prospectively enrolled. Blood cultures were incubated, and pathogens in positive cultures were determined by MALDI-TOF. An immunological assay for blood cell components was conducted by flow cytometry with antibody cocktails. The diagnostic criteria for neonatal sepsis were identified by qualified neonatologists and included both clinical sepsis and/or positive blood culture. The analyzed infants were grouped into non-septic infants, surviving septic infants, and deceased septic infants. The results showed that deceased septic newborns had a lower level of CD8+ lymphocytes and higher PDL-1 expression in comparison with surviving septic newborns. PDL-1 expression on CD8+ T cells might play an immunosuppressive role during neonatal sepsis and might be used as a laboratory biomarker in the future.

Bioinformatic Analysis and Machine Learning Methods in Neonatal Sepsis: Identification of Biomarkers and Immune Infiltration

“…After the onset of sepsis, the activity and toxicity of NK cells were further reduced, leading to disease progression and adverse outcomes [41]. In addition, PD-1 exerted an immunosuppressive effect in NS by downregulating CD8+ T cell activity during the inflammatory response and exacerbating disease progression, due to the acquired immune deficiency of neonates [42]. However, the association of CD4 T cells with NS has not been reported and thus requires further investigation.…”

Identification of new biomarkers and immune infiltration characteristics of sepsis in very low birth weight infants

“…Circulating regulatory T cells induce immunosuppression through upregulation of tumor necrosis factor receptor type 2 expression in patients with septic shock [ 32 ]. In addition, due to the insufficient acquired immunity of newborns, PD-1 exerts an immunosuppressive effect on neonatal sepsis by downregulating CD8+ T cells activity during the inflammatory response, aggravating disease progression [ 33 ]. Finally, we investigated the correlation between infiltrating immune cells and diagnostic markers.…”

Биологические Маркеры Сепсиса

“…Выявлено, что у новорожденных, умерших от сепсиса, уровень лимфоцитов CD8 + был ниже, а экспрессия белка PD-L1 (Programmed Cell Death Ligand 1) выше, чем у выживших. На основании этих результатов предложено использовать экспрессию PD-L1 на CD8 + Т клетках в качестве биомаркера прогноза сепсиса у новорожденных [17].…”