Delayed increased S100A9 mRNA predicts hospital-acquired infection after septic shock

Introduction

Septic shock (SS) remains a serious disease with high mortality and increased risk of hospital-acquired infection (HAI). Access to biomarkers assessing prognosis of these outcomes is of utmost importance in order to select patients for future therapeutic strategies. Alarmins are normal cell constituents that can be released into the extracellular milieu during states of cellular stress and subsequently activate the innate immune system. Several alarmins of the S100 family are released by phagocytes in response to cell stress, recognized by RAGE and/or TLR4 on monocytes and therefore highlight as relevant mediators in sepsis pathophysiology. Among them, S100A8 and S100A9 exist mainly as a heterodimer called calprotectin. However, several studies suggest independent functioning of S100A9, making it an interesting candidate biomarker in septic syndromes.

Objective

To assess capacity of S100A9 mRNA in whole blood from SS patients to predict survival and the occurrence of HAI.

Methods

The authors conducted a cohort study. This study was conducted in two ICUs in Lyon University Hospital. The study included 166 SS patients and 44 healthy volunteers. PAXgene blood samples were obtained regularly in the course of the syndrome for S100A9 gene expression analysis using qRT-PCR.

Results

The overall mortality was 38% and the mean SAPS II on shock onset was 52. Thirty-seven patients (23%) experienced at least one HAI after septic shock. We found that S100A9 mRNA levels at days 1 to 3 after the onset of shock were significantly higher in SS patients compared with healthy volunteers (median: 1,460 vs. 16,620; P < 0.0001) but not significantly different in nonsurviving versus surviving patients (median: 18,070 vs. 16,310; P = 0.1278). In contrast, systemic S100A9 mRNA levels measured at days 7 to 10 were significantly higher in the group of patients that were going to develop HAI compared with patients that were not (median: 10,140 vs. 7,160; P = 0.009). Multivariate analysis showed that the S100A9 mRNA level at days 7 to 10 after the onset of septic shock significantly increases the probability of HAI with odd ratios of 1.12 per unit (P = 0.0054).

Conclusion

Our results showed that S100A9 mRNA is overexpressed in blood from SS. We showed that its persistent overexpression over time is associated with the occurrence of secondary HAI. This biomarker may be of major interest in identifying patients at increased HAI risk who could benefit from either targeted therapy aimed at restoring immune functions (in case of associated immunosuppression) or reinforced antibiotherapy and measures against cross-transmission.