Evidence map›Paper›PMID 36384965›Full record

ArticleLupus science & medicine2022

Associations between circulating interferon and kynurenine/tryptophan pathway metabolites: support for a novel potential mechanism for cognitive dysfunction in SLE.

Erik W Anderson, Ying Jin, Andrew Shih, Arnon Arazi, Sara Goodwin, Julien Roeser, Richard A Furie, Cynthia Aranow, Bruce Volpe, Betty Diamond and 1 more

Open access · goldAbstract read
In one paragraph

Article in Lupus science & medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.1field-weighted citation impact, top 25% 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, 20 citations in OpenAlex.

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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

11 authors at 4 institutions in 1 country.

Erik W AndersonInstitute of Molecule Medicine, The Feinstein Institutes for Medical Research, Manhasset, New York, USA eanderson22@northwell.edu.ORCID 0000-0003-3154-9648
Ying JinCold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
Andrew ShihGenomics and Human Genetics, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Arnon AraziInstitute of Molecule Medicine, The Feinstein Institutes for Medical Research, Manhasset, New York, USA.
Sara GoodwinCold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
Julien RoeserCharles River Laboratories, South San Francisco, California, USA.
Richard A FurieInstitute of Molecule Medicine, The Feinstein Institutes for Medical Research, Manhasset, New York, USA.ORCID 0000-0001-6712-1585
Cynthia AranowInstitute of Molecule Medicine, The Feinstein Institutes for Medical Research, Manhasset, New York, USA.ORCID 0000-0001-9299-0053
Bruce VolpeInstitute of Molecule Medicine, The Feinstein Institutes for Medical Research, Manhasset, New York, USA.
Betty DiamondInstitute of Molecule Medicine, The Feinstein Institutes for Medical Research, Manhasset, New York, USA.ORCID 0000-0002-3250-3804
Meggan MackayInstitute of Molecule Medicine, The Feinstein Institutes for Medical Research, Manhasset, New York, USA.
Feinstein Institute for Medical Research · USCold Spring Harbor Laboratory · USCharles River Laboratories (United States) · USNorthwell Health · US

Funding

Single-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI John Edward Moses · 1987 to 2026
$118.9M
The Monoclonal Antibody and Reagent CoreP01AI073693 · NIAID · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI Cynthia Aranow · 2008 to 2026
$45.8M
The Development and Optimization of Long-Read Sequencing Applications to Cancer Genomics in a Core SettingR50CA243890 · NCI · COLD SPRING HARBOR LABORATORY · PI GOODWIN, SARA · 2019 to 2025
$920k
NCI NIH HHS P30 CA045508NCI NIH HHS R50 CA243890NIAID NIH HHS P01 AI073693
6 · The paper itself

Abstract

objectiveQuinolinic acid (QA), a kynurenine (KYN)/tryptophan (TRP) pathway metabolite, is an N-methyl-D-aspartate receptor agonist that can produce excitotoxic neuron damage. Type I and II interferons (IFNs) stimulate the KYN/TRP pathway, producing elevated QA/kynurenic acid (KA), a potential neurotoxic imbalance that may contribute to SLE-mediated cognitive dysfunction. We determined whether peripheral blood interferon-stimulated gene (ISG) expression associates with elevated serum KYN:TRP and QA:KA ratios in SLE.

methodsISG expression (whole-blood RNA sequencing) and serum metabolite ratios (high-performance liquid chromatography) were measured in 72 subjects with SLE and 73 healthy controls (HCs). ISG were identified from published gene sets and individual IFN scores were derived to analyse associations with metabolite ratios, clinical parameters and neuropsychological assessments. SLE analyses were grouped by level of ISG expression ('IFN high', 'IFN low' and 'IFN similar to HC') and level of monocyte-associated gene expression (using CIBERSORTx).

resultsSerum KYN:TRP and QA:KA ratios were higher in SLE than in HC (p<0.01). 933 genes were differentially expressed ≥2-fold in SLE versus HC (p<0.05). 70 of the top 100 most highly variant genes were ISG. Approximately half of overexpressed genes that correlated with KYN:TRP and QA:KA ratios (p<0.05) were ISG. In 36 IFN-high subjects with SLE, IFN scores correlated with KYN:TRP ratios (p<0.01), but not with QA:KA ratios. Of these 36 subjects, 23 had high monocyte-associated gene expression, and in this subgroup, the IFN scores correlated with both KY:NTRP and QA:KA ratios (p<0.05).

conclusionsHigh ISG expression correlated with elevated KYN:TRP ratios in subjects with SLE, suggesting IFN-mediated KYN/TRP pathway activation, and with QA:KA ratios in a subset with high monocyte-associated gene expression, suggesting that KYN/TRP pathway activation may be particularly important in monocytes. These results need validation, which may aid in determining which patient subset may benefit from therapeutics directed at the IFN or KYN/TRP pathways to ameliorate a potentially neurotoxic QA/KA imbalance.

Indexed as

Cognitive DysfunctionLupus Erythematosus, SystemicHumansInterferonsKynurenic AcidKynurenineQuinolinic AcidTryptophanInterferonsKynurenic AcidKynurenineQuinolinic AcidTryptophanAutoimmunityInterferon Type ILupus Erythematosus, Systemic

Identifiers

PMID36384965
PMCPMC9670923
OpenAlexW4309324242

What OpenQuestion holds

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LicenceCC BY-NC
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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.