Evidence map›Paper›PMID 40394087›Full record

ArticleNature communications2025

In depth transcriptomic profiling defines a landscape of dysfunctional immune responses in patients with VEXAS syndrome.

Hiroki Mizumaki, Shouguo Gao, Zhijie Wu, Fernanda Gutierrez-Rodrigues, Massimiliano Bissa, Xingmin Feng, Emma M Groarke, Haoran Li, Lemlem Alemu, Diego Quinones Raffo and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Myelodysplasia in VEXAS syndrome.Blood advances · 2026
    Review
  2. SomaticBlood neoplasia · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. VEXAS syndrome.Nature reviews. Disease primers · 2026
    Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
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

16 authors.

Hiroki Mizumaki *Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Shouguo Gao *Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-8275-0598
Zhijie WuHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. zhijie.wu@nih.gov.ORCID http://orcid.org/0000-0003-3984-0819
Fernanda Gutierrez-RodriguesHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Massimiliano BissaAnimal Models and Retroviral Vaccines Section, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-3455-3992
Xingmin FengHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Emma M GroarkeHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-4648-5926
Haoran LiHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-1304-5334
Lemlem AlemuHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Diego Quinones RaffoHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Ivana DardenHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Sachiko KajigayaHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Peter C GraysonVasculitis Translational Research Program, National Institute of Arthritis and Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Genoveffa FranchiniAnimal Models and Retroviral Vaccines Section, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-2851-6589
Neal S YoungHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. youngns@nhlbi.nih.gov.
Bhavisha A PatelHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is caused by inactivating somatic mutations in the UBA1 gene. Here, we characterize the immunological landscape of VEXAS syndrome by performing multi-omics single-cell RNA analysis, cytokine multiplex assays, and in vitro functional assays on patients' peripheral blood. Our data reveals a broad immune system activation with upregulation of multiple inflammatory response pathways and proinflammatory cytokines. Unexpectedly, we find that monocytes have dysfunctional features irrespective of UBA1 mutation status, exhibiting impaired efferocytosis and blunted cytokine production in vitro. In contrast, UBA1-mutated NK cells show an upregulation of the inflammation pathways and enhanced cytotoxicity. Within the lymphocyte subsets, predominantly UBA1 wild-type, we identify clonal expansion of effector memory CD8

Indexed as

Genetic Diseases, X-LinkedUbiquitin-Activating EnzymesAdultB-LymphocytesCD8-Positive T-LymphocytesCytokinesFemaleGene Expression ProfilingHumansImmunity, InnateKiller Cells, NaturalMaleMonocytesMutationMyelodysplastic SyndromesSingle-Cell AnalysisCytokinesUBA1 protein, humanUbiquitin-Activating Enzymes

Identifiers

PMID40394087
PMCPMC12092610

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.