Kinetics of molecular patterns captured by mannose-binding lectin in septic shock correlate with clinical outcome: a monocentric prospective observational study

Abstract

Abstract Background Various serum biomarkers and scoring systems are currently employed to manage septic critically ill patients. However, a paucity of biomarker evidence facilitates sepsis identification or prognosis. Mannose-binding lectin (MBL) is the main circulating protein in innate immunity. It acts as a broad-spectrum recognition molecule that binds most pathogens, along with their breakdown products and cell debris. We report results of an original approach dosing molecular patterns captured by FcMBL, an engineered version of MBL, in patients with septic shock. This study aimed at evaluating molecular patterns kinetics to assess their potential contribution to the clinical management of critically ill patients suffering from septic shock. Results This monocentric, prospective, observational study was conducted on adults admitted to the intensive care unit (ICU) for septic shock. Using magnetic microbeads coated with FcMBL, we quantified molecular patterns captured in blood and analyzed their kinetics for 5 days. Pathogen-associated molecular patterns (PAMP) levels were sampled at 6-h intervals over the first 24 h of ICU admission, then at 12 h intervals on Day 2, and then daily through Day 5. To align the data from the real time of admission to the ICU, the “Serial Measurements” module in MedCalc ® software enabled the incorporation of advanced methods, such as mixed models. Outcomes were the persistence of sepsis after Day 5 and adherence to routine sepsis metrics. Thirty-nine patients were included in the study. At Day 5, 21 patients had recovered from sepsis with a sequential organ failure assessment (SOFA) score < 2, while 18 were not. The initial values of PAMP yielded a median concentration of 5 ng/mL. The peak concentration was observed at 9 ng/mL, with a median delay of 24 h. Significant differences were observed in kinetic curves according to the SOFA score at Day 5, with a notable delay in time to peak (Tmax) for the prolonged sepsis group (Hour 48) compared to the short-term sepsis group (Hour 18) (p < 0.001). Compared to standard biomarkers, Tmax PAMP was the most discriminative factor for an unfavorable outcome. Conclusions Molecular pattern levels captured by FcMBL during septic shock exhibited large inter-patient variability, suggesting values depend on numerous parameters. The signal’s kinetics demonstrated predictive value and may contribute to clinical management. Trial registration : clinicaltrials, NCT03457038, Registered 15 October 2017, https://clinicaltrials.gov/study/NCT03457038

Affiliated Institutions

• Digestive Health Research Institute FR
• Université Toulouse III - Paul Sabatier FR
• Hôpital Purpan FR
• Harvard University US
• Inserm FR
• Centre Hospitalier Universitaire de Toulouse FR
• Université Fédérale de Toulouse Midi-Pyrénées FR

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