Evidence map›Paper›PMID 33863324›Full record

ArticleBMC medical genomics2021

Transcriptomic biomarker pathways associated with death in HIV-infected patients with cryptococcal meningitis.

Irina Vlasova-St Louis, Abdu K Musubire, David B Meya, Henry W Nabeta, Hesham Mohei, David R Boulware, Paul R Bohjanen

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC medical genomics, 2021. 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
1.2field-weighted citation impact, top 22% of its field
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, 10 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Targeting inflammasomes as a therapeutic potential for HIV/AIDS.Cellular and molecular life sciences : CMLS · 2025
    Review
  6. Molecular Diagnostics ofDiseases (Basel, Switzerland) · 2024
    Review
  7. Article
  8. Review
  9. Article
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

7 authors at 2 institutions in 2 countries.

Irina Vlasova-St LouisDepartment of Medicine, University of Minnesota, Minneapolis, MN, USA. irinastl@umn.edu.ORCID 0000-0003-0795-4723
Abdu K MusubireInfectious Disease Institute, Makerere University, Kampala, Uganda.
David B MeyaInfectious Disease Institute, Makerere University, Kampala, Uganda.
Henry W NabetaInfectious Disease Institute, Makerere University, Kampala, Uganda.
Hesham MoheiDepartment of Medicine, University of Minnesota, Minneapolis, MN, USA.
David R BoulwareDepartment of Medicine, University of Minnesota, Minneapolis, MN, USA.
Paul R BohjanenDepartment of Medicine, University of Minnesota, Minneapolis, MN, USA.
University of Minnesota · USMakerere University · UG

Funding

Trial for the Optimal Timing of HIV Therapy after Cryptococcal MeningitisU01AI089244 · NIAID · UNIVERSITY OF MINNESOTA · PI BOULWARE, DAVID R · 2010 to 2014
$7.6M
Outcomes of Cryptococcal Meningitis in UgandaK24AI096925 · NIAID · UNIVERSITY OF MINNESOTA · PI BOHJANEN, PAUL R · 2011 to 2015
$1.0M
NIAID NIH HHS K24 AI096925NIAID NIH HHS U01 AI089244NIH HHS AI096925NIH HHS U01AI089244
6 · The paper itself

Abstract

backgroundCryptococcal meningitis (CM) is a major cause of death in HIV-infected patients in sub-Saharan Africa. Many CM patients experience cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS), which is often fatal. We sought to identify transcriptomic biomarker pathways in peripheral blood that are associated with or predict the development of death or fatal C-IRIS among patients with CM who were enrolled in the Cryptococcal Optimal ART Timing Trial.

methodsWe assessed peripheral blood gene expression using next-generation RNA sequencing in 4 groups of patients with CM: (1) no C-IRIS or Death; (2) C-IRIS survivors; (3) fatal C-IRIS; (4) Death without C-IRIS. Gene expression was assessed at the time of ART initiation, at 1, 4, and 8 weeks on ART, and at the time of C-IRIS events.

resultsWe identified 12 inflammatory and stress response pathways, including interferon type 1 signaling, that were upregulated at the time of ART initiation in patients with future fatal C-IRIS, as compared with survivors. The upregulation of transcripts involved in innate immunity (inflammasome, Toll-like receptor signaling), was observed at the time of fatal or nonfatal C-IRIS events. At the time of fatal C-IRIS events, numerous transcripts within fMLP, Rho family GTPases, HMGB1, and other acute phase response signaling pathways were upregulated, which reflects the severity of inflammation and systemic oxidative stress. Patients who died without recognized C-IRIS also had increased expression of pathways associated with oxidative stress and tissue damage.

conclusionsOur results showed that overactivated innate immunity, involving Toll-like receptor/inflammasome pathways, and inflammation-induced oxidative stress, are associated with fatal outcomes. The results of this study provide insight into the molecular drivers of death and fatal C-IRIS to inform future diagnostic test development or guide targeted treatments.

Indexed as

BiomarkersHIV InfectionsMeningitis, CryptococcalTranscriptomeAdultFemaleGene Expression ProfilingHumansImmune Reconstitution Inflammatory SyndromeMaleBiomarkersAIDS/HIVCryptococcal meningitis IRISFatal immune reconstitution inflammatory syndromeTranscriptomic biomarkers

Identifiers

PMID33863324
PMCPMC8052789
OpenAlexW3110780961

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.