# Evaluation of Immune Dysregulation in Sepsis with a Composite Marker Gene Panel

## TL;DR

This study identifies immune dysregulation patterns in sepsis using a gene panel, showing how these patterns can predict patient outcomes and guide treatment.

## Contribution

A novel composite gene panel is introduced to monitor immune dysregulation in sepsis and predict survival outcomes.

## Key findings

- Sepsis is marked by activation of NDrG genes and suppression of HLAd and LYMd genes.
- The (NDrG-HLAd) ratio combined with SOFA score predicted 90% of survivors with low false positives.
- Immune gene dysregulation reversed in ICU-treated sepsis patients, especially those with better outcomes.

## Abstract

Background: Dysregulated host response to infection plays vital roles in the high mortality rate of sepsis. Better understanding of the dysregulated host response is required for the improved management of sepsis. Methods: In this work, we conducted side-by-side comparison of several components of host immunity in sepsis with a composite marker gene panel. This gene panel consisted of five sets of marker genes, including the NDrG gene set for neutrophil degranulation-related genes, the ISGa gene set for type I interferon signaling, the GBPs gene set for type II interferon signaling, the HLAd gene set for major histocompatibility (MHC) class II, and the LYMd gene set for lymphocytes and dendritic cells. Seven relevant transcriptome datasets were used for the evaluation. Results: It was found that sepsis was characterized by simultaneous activation of the NDrG gene set and suppression of the HLAd and LYMd gene sets. In contrast, both activation and suppression of the ISGa and GBPs gene sets were observed in sepsis. Compared to sepsis patients with hypo-inflammation, those with hyper-inflammation displayed higher values of NDrG and lower values of HLAd and LYMd. Reversal of gene dysregulation was observed in the NDrG, HLAd and LYMd gene sets for sepsis patients after treatment at intensive care unit (ICU), especially for those who responded better to the treatment. In a cohort of sepsis patients admitted to the ICU, the initial expression values of the NDrG, HLAd and LYMd gene sets were associated with the outcome. Notably, all patients with (NDrG-HLAd) < 1.5 survived, accounting for 75% of the survivors (45 out of 60). A simple combination of the (NDrG-HLAd) value and the sequential organ failure assessment (SOFA) score could identify 90% of the survivors with 3.5% false positive rate. Conclusions: Overall, this composite gene panel is applicable to the serial monitoring of immune dysregulation in sepsis. It also suggests that the NDrG and HLAd gene sets may be promising targets for immune modulation in sepsis.