Evidence map›Paper›PMID 31877114›Full record

ArticleJCI insight2020

IRF5 genetic risk variants drive myeloid-specific IRF5 hyperactivation and presymptomatic SLE.

Dan Li, Bharati Matta, Su Song, Victoria Nelson, Kirsten Diggins, Kim R Simpfendorfer, Peter K Gregersen, Peter Linsley, Betsy J Barnes

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
–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

30 citing papers in PubMed.

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  17. Advances in the Pathogenesis and Treatment of Systemic Lupus Erythematosus.International journal of molecular sciences · 2023
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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

9 authors.

Dan LiCenter for Autoimmune, Musculoskeletal and Hematopoietic Diseases, The Feinstein Institutes for Medical Research, Manhasset, New York, USA.
Bharati MattaCenter for Autoimmune, Musculoskeletal and Hematopoietic Diseases, The Feinstein Institutes for Medical Research, Manhasset, New York, USA.
Su SongCenter for Autoimmune, Musculoskeletal and Hematopoietic Diseases, The Feinstein Institutes for Medical Research, Manhasset, New York, USA.
Victoria NelsonCenter for Autoimmune, Musculoskeletal and Hematopoietic Diseases, The Feinstein Institutes for Medical Research, Manhasset, New York, USA.
Kirsten DigginsSystems Immunology Division, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
Kim R SimpfendorferRobert S. Boas Center for Genomics and Human Genetics, The Feinstein Institutes for Medical Research, Manhasset, New York, USA.
Peter K GregersenRobert S. Boas Center for Genomics and Human Genetics, The Feinstein Institutes for Medical Research, Manhasset, New York, USA.
Peter LinsleySystems Immunology Division, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
Betsy J BarnesCenter for Autoimmune, Musculoskeletal and Hematopoietic Diseases, The Feinstein Institutes for Medical Research, Manhasset, New York, USA.

Funding

IRF5-TNPO3 locus: Inclusion of TNPO3 as a unique regulator of IRF5 expression anR21AR065959 · NIAMS · RBHS-NEW JERSEY MEDICAL SCHOOL · PI BARNES, BETSY J · 2014 to 2015
$385k
NIAMS NIH HHS R21 AR065959
6 · The paper itself

Abstract

Genetic variants within or near the interferon regulatory factor 5 (IRF5) locus associate with systemic lupus erythematosus (SLE) across ancestral groups. The major IRF5-SLE risk haplotype is common across populations, yet immune functions for the risk haplotype are undefined. We characterized the global immune phenotype of healthy donors homozygous for the major risk and nonrisk haplotypes and identified cell lineage-specific alterations that mimic presymptomatic SLE. Contrary to previous studies in B lymphoblastoid cell lines and SLE immune cells, IRF5 genetic variants had little effect on IRF5 protein levels in healthy donors. Instead, we detected basal IRF5 hyperactivation in the myeloid compartment of risk donors that drives the SLE immune phenotype. Risk donors were anti-nuclear antibody positive with anti-Ro and -MPO specificity, had increased circulating plasma cells and plasmacytoid dendritic cells, and had enhanced spontaneous NETosis. The IRF5-SLE immune phenotype was conserved over time and probed mechanistically by ex vivo coculture, indicating that risk neutrophils are drivers of the global immune phenotype. RNA-Seq of risk neutrophils revealed increased IRF5 transcript expression, IFN pathway enrichment, and decreased expression of ROS pathway genes. Altogether, the data support that individuals carrying the IRF5-SLE risk haplotype are more susceptible to environmental/stochastic influences that trigger chronic immune activation, predisposing to the development of clinical SLE.

Indexed as

Genetic VariationCell LineFemaleGenetic Predisposition to DiseaseGenotypeHaplotypesHumansInterferon Regulatory FactorsLupus Erythematosus, SystemicLymphocytesMaleNeutrophilsRisk FactorsInterferon Regulatory FactorsIRF5 protein, humanAutoimmune diseasesGeneticsImmunology

Identifiers

PMID31877114
PMCPMC7098722

What OpenQuestion holds

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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.