Serum TLR2, TLR4, TLR2/TLR4 Ratio, and ESM1 in Sepsis: A Single-Center Prospective Observational Study of Diagnostic and Prognostic Associations

Background/Objectives: Sepsis remains a major cause of morbidity and mortality, and reliable diagnostic and prognostic biomarkers are needed. This study investigated the diagnostic and prognostic associations of endothelial cell-specific molecule-1 (ESM1), toll-like receptor (TLR)2, TLR4, and the TLR2/TLR4 ratio in sepsis. Methods: In this single-center prospective observational study, serum biomarker levels were measured in 60 patients with sepsis and 23 ambulatory controls and analyzed for associations with the presence of sepsis and in-hospital mortality. Demographic characteristics and comorbidities were comparable between groups. Results: No significant differences were observed in ESM1, TLR4, or the TLR2/TLR4 ratio between groups (p > 0.05). TLR2 levels were lower in patients with sepsis than in controls (median [IQR]: 0.551 [1.508] vs. 1.394 [8.606], respectively; p = 0.056), without reaching statistical significance. Receiver operating characteristic analysis yielded an AUC of 0.636 (p = 0.080) for TLR2, with 91.7% sensitivity and 47.8% specificity at a cut-off of ≤3.2129. In-hospital mortality occurred in 36.7% of patients. Serum creatinine levels were higher in non-survivors than survivors (median: 2.30 vs. 0.89 mg/dL; p = 0.039), whereas no significant associations with mortality were observed for demographic characteristics, clinical findings, other laboratory parameters, or biomarker levels. Conclusions: TLR2 levels were numerically lower in sepsis, but the difference was not statistically significant. Its diagnostic utility requires validation against non-infectious systemic inflammation in clinically relevant control populations. No significant diagnostic or prognostic associations were detected for ESM1, TLR4, or the TLR2/TLR4 ratio in this cohort.