Frontiers in immunology · 2025
Diagnostic efficiency of inflammatory signatures to distinguish isolated candidemia from candidemia with bacterial co-infection.
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Mnichowska-Polanowska Magdalena, Grygorcewicz Bartłomiej, Dołęgowska Barbara, Boroń Agnieszka, Michnowska Agata, Jarosz Konrad, Adamowicz Magdalena, Wojciuk Bartosz
Аннотация
INTRODUCTION: To identify the differences in inflammatory response between critically ill patients responding to combined bacterial-fungal sepsis and those with isolated fungal sepsis.
METHODS: A retrospective case-control study compared ICU patients who were exposed (n=24) and unexposed (n=20) to candidemia. Two exposure modes were analyzed: isolated candidemia (C; n=12) versus candidemia with bacterial co-infection (BC; n=12). Targeted proximity extension assay (PEA) was used to examine differences in serum inflammatory proteome between groups. Differential inflammatory proteins served as input for a logistic regression model to validate their effectiveness in discrimination.
RESULTS: Two major clusters-candidemia cases and controls-were identified based on differential protein expression analysis. In five-fold cross-validation, LAP-TGF beta-1 was identified as the main driver, effectively distinguishing isolated candidemia [AUC 0.95; 95% CI 0.853-1.000]. TRANCE and IL-17C showed potential as a diagnostic signature indicating bacterial co-infection in the context of candidemia.
DISCUSSION: The three-protein logistic regression panel (LAP-TGF beta-1, TRANCE and IL-17C) differentiated cases with isolated candidemia from those with candidemia and bacterial co-infection [AUC 0.82; 95% CI 0.629-0.968]. A three-protein inflammatory signature distinguished isolated fungal sepsis from combined bacterial-fungal sepsis. This study is the first to explore the inflammatory response to differentiate isolated candidemia from candidemia with bacterial co-infection.
METHODS: A retrospective case-control study compared ICU patients who were exposed (n=24) and unexposed (n=20) to candidemia. Two exposure modes were analyzed: isolated candidemia (C; n=12) versus candidemia with bacterial co-infection (BC; n=12). Targeted proximity extension assay (PEA) was used to examine differences in serum inflammatory proteome between groups. Differential inflammatory proteins served as input for a logistic regression model to validate their effectiveness in discrimination.
RESULTS: Two major clusters-candidemia cases and controls-were identified based on differential protein expression analysis. In five-fold cross-validation, LAP-TGF beta-1 was identified as the main driver, effectively distinguishing isolated candidemia [AUC 0.95; 95% CI 0.853-1.000]. TRANCE and IL-17C showed potential as a diagnostic signature indicating bacterial co-infection in the context of candidemia.
DISCUSSION: The three-protein logistic regression panel (LAP-TGF beta-1, TRANCE and IL-17C) differentiated cases with isolated candidemia from those with candidemia and bacterial co-infection [AUC 0.82; 95% CI 0.629-0.968]. A three-protein inflammatory signature distinguished isolated fungal sepsis from combined bacterial-fungal sepsis. This study is the first to explore the inflammatory response to differentiate isolated candidemia from candidemia with bacterial co-infection.