Two blood gene signatures track sepsis outcomes

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In UK ICU adults with pneumonia sepsis, leukocyte transcriptomes split into SRS1 (immunosuppressed, ~41%) and SRS2; SRS1 had roughly 2–3× higher 14-day mortality, and a 7-gene set classified the groups.

Source

Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study

Davenport EE, Burnham KL, Radhakrishnan J, et al. · The Lancet. Respiratory medicine · 2016

doi.org/10.1016/s2213-2600(16)00046-1 Read the full paper ↗699 citationscc by

Study at a glance

Design: Cohort — GAinS prospective ICU transcriptomic discovery + validation
N: N=265 · Discovery cohort; validation n=106 further ICU patients
Population: UK ICU adults with community-acquired pneumonia sepsis and organ dysfunction
Outcome: Transcriptomic sepsis response signatures (SRS1/SRS2) and 14-day mortality

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What they did

In the GAinS study, authors profiled peripheral-blood leukocyte gene expression in a prospective discovery cohort of 265 UK ICU adults with community-acquired pneumonia sepsis and organ dysfunction, then validated in 106 further patients. They related transcriptomic subgroups to outcomes and mapped expression quantitative trait loci (eQTL).

What they found

Unsupervised clustering defined two sepsis response signatures, SRS1 and SRS2. SRS1 (~41% of discovery patients) showed an immunosuppressed phenotype (endotoxin tolerance, T-cell exhaustion, HLA class II downregulation) and higher 14-day mortality (discovery HR 2.4; validation HR 2.8). A predictive set of seven genes classified SRS membership.

The limits

What it doesn't show

Does not prove that assigning SRS at the bedside and treating differently improves survival in a randomized trial. The discovery setting is pneumonia-driven ICU sepsis in UK adults—not every infection source or age group. Genetic eQTL findings explain expression variation; they are not prescriptions for IL-6 drugs.

Key terms

SRS1 / SRS2: Transcriptomic sepsis response signatures from blood leukocytes after ICU admission.
Immunosuppressed phenotype: SRS1 features including endotoxin tolerance, T-cell exhaustion, and HLA class II downregulation.
eQTL: Expression quantitative trait loci linking genetic variants to gene-expression differences.
GAinS: UK Genomic Advances in Sepsis ICU cohort study that supplied discovery and validation patients.
Seven-gene classifier: Predictive gene set that assigned patients to SRS1 versus SRS2.

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What does SRS1 mark in this study?

Common questions

What is SRS1?

A blood transcriptomic sepsis response signature linked to an immunosuppressed phenotype and higher early mortality.

How common was SRS1 in discovery?

About 108 of 265 patients (41%).

What mortality contrast did they report?

SRS1 had higher 14-day mortality than SRS2 (discovery HR 2.4; validation HR 2.8).

Who was studied?

Adult UK ICU patients with community-acquired pneumonia sepsis and organ dysfunction (265 discovery + 106 validation).

Is this a treatment trial?

No — it defines prognostic immune-response subgroups and genetic regulators of expression, not a tested therapy protocol.