Evidence map›Paper›PMID 40532705›Full record

ArticleImmunity2025

A conserved immune dysregulation signature is associated with infection severity, risk factors prior to infection, and treatment response.

Ananthakrishnan Ganesan, Andrew R Moore, Hong Zheng, Jiaying Toh, Michael Freedman, Andrew T Magis, James R Heath, Purvesh Khatri

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Guideline
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Ananthakrishnan GanesanInstitute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA; Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA, USA.
Andrew R MooreInstitute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA; Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA, USA.
Hong ZhengInstitute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA; Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA, USA.
Jiaying TohInstitute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA; Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA, USA.
Michael FreedmanInstitute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA; Division of Pediatric Critical Care, Stanford University, Stanford, CA, USA.
Andrew T MagisInstitute of Systems Biology, Seattle, WA, USA.
James R HeathInstitute of Systems Biology, Seattle, WA, USA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.
Purvesh KhatriInstitute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA; Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA, USA. Electronic address: pkhatri@stanford.edu.

Funding

Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5M
NIAID NIH HHS U19 AI057229
6 · The paper itself

Abstract

Older age, being male, obesity, smoking, and comorbidities (e.g., diabetes, asthma) are associated with an increased risk for severe infections. We hypothesized that there is a conserved common immune dysregulation across these risk factors. We integrated single-cell and bulk transcriptomic data and proteomic data from 12,026 blood samples across 68 cohorts to test this hypothesis. We found that our previously described 42-gene Severe-or-Mild (SoM) signature was associated with each of these risk factors prior to infection. Furthermore, this conserved immune signature was modifiable using immunomodulatory drugs and lifestyle changes. The SoM score predicted the individuals with sepsis who would be harmed by hydrocortisone treatment and individuals with asthma who would not respond to monoclonal antibody treatment. Finally, the SoM score was associated with all-cause mortality. The SoM signature has the potential to redefine the immunologic framing of the baseline immune state and response to chronic, subacute, and acute illnesses.

Indexed as

InfectionsAdultAgedAsthmaFemaleGene Expression ProfilingHumansMaleMiddle AgedProteomicsRisk FactorsSeverity of Illness IndexTranscriptomeall-cause mortalityconserved immune dysregulationimpact of lifestyle changesmulti-cohort analysismulti-omicsrisk factors for severe infectionssepsistreatment response prediction

Identifiers

PMID40532705
PMCPMC13109016

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.