Evidence map›Paper›PMID 22300536›Full record

ArticleArthritis research & therapy2012

Specific post-translational histone modifications of neutrophil extracellular traps as immunogens and potential targets of lupus autoantibodies.

Chih Long Liu, Stephanie Tangsombatvisit, Jacob M Rosenberg, Gil Mandelbaum, Emily C Gillespie, Or P Gozani, Ash A Alizadeh, Paul J Utz

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed, 2 pooled it
7.9field-weighted citation impact, top 2% 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

113 citing papers in PubMed, 2 syntheses or guidelines pooled it, 170 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Regulation of histones in thromboinflammation.Frontiers in immunology · 2026
    Review
  5. Article
  6. A Web of Challenges: The Therapeutic Struggle to Target NETs in Disease.International journal of molecular sciences · 2025
    Review
  7. Article
  8. Article
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  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Felty's syndrome.Frontiers in medicine · 2023
    Review
  17. [The characteristics of neutrophil extracellular traps produced by all-trans retinoic acid-induced dHL-60 under PMA stimulation].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2022
    Article
  18. Article
  19. Review
  20. Neutrophils and Asthma.Diagnostics (Basel, Switzerland) · 2022
    Review

53 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Chih Long LiuDepartment of Medicine, Division of Immunology and Rheumatology, Stanford School of Medicine, 269 Campus Drive, Stanford, California 94305, USA.
Stephanie Tangsombatvisit
Jacob M Rosenberg
Gil Mandelbaum
Emily C Gillespie
Or P Gozani
Ash A Alizadeh
Paul J Utz
Stanford Medicine · USStanford University · USUniversity of Minnesota Medical Center · US

Funding

Training Program in Adult and Pediatric RheumatologyT32AR050942 · NIAMS · STANFORD UNIVERSITY · PI LEWIS, DAVID BRAM, ROBINSON, WILLIAM H · 2005 to 2025
$6.6M
Function of PHD Domain Proteins in Chromatin RegulationR01GM079641 · NIGMS · STANFORD UNIVERSITY · PI GOZANI, OR P. · 2007 to 2020
$4.5M
Th17 lymphocytes in human autoimmune diseasesU19AI082719 · NIAID · STANFORD UNIVERSITY · PI FATHMAN, CHARLES GARRISON · 2009 to 2013
$3.4M
Profiling Epigenetic Biomarkers for the Study and Treatment of LupusF32AI080086 · NIAID · STANFORD UNIVERSITY · PI LIU, CHIH LONG · 2009 to 2010
$108k
Canadian Institutes of Health Research 2 OR-92141NIAID NIH HHS 5 U19-AI082719NIAID NIH HHS AI-080086-02NIAMS NIH HHS T32 AR050942NIGMS NIH HHS R01 GM079641
6 · The paper itself

Abstract

introductionAutoreactivity to histones is a pervasive feature of several human autoimmune disorders, including systemic lupus erythematosus (SLE). Specific post-translational modifications (PTMs) of histones within neutrophil extracellular traps (NETs) may potentially drive the process by which tolerance to these chromatin-associated proteins is broken. We hypothesized that NETs and their unique histone PTMs might be capable of inducing autoantibodies that target histones.

methodsWe developed a novel and efficient method for the in vitro production, visualization, and broad profiling of histone-PTMs of human and murine NETs. We also immunized Balb/c mice with murine NETs and profiled their sera on autoantigen and histone peptide microarrays for evidence of autoantibody production to their immunogen.

resultsWe confirmed specificity toward acetyl-modified histone H2B as well as to other histone PTMs in sera from patients with SLE known to have autoreactivity against histones. We observed enrichment for distinctive histone marks of transcriptionally silent DNA during NETosis triggered by diverse stimuli. However, NETs derived from human and murine sources did not harbor many of the PTMs toward which autoreactivity was observed in patients with SLE or in MRL/lpr mice. Further, while murine NETs were weak autoantigens in vivo, there was only partial overlap in the immunoglobulin G (IgG) and IgM autoantibody profiles induced by vaccination of mice with NETs and those seen in patients with SLE.

conclusionsIsolated in vivo exposure to NETs is insufficient to break tolerance and may involve additional factors that have yet to be identified.

Indexed as

AnimalsApoptosisAutoantibodiesAutoantigensCell LineCells, CulturedChromatinCytoplasmic GranulesEpigenomicsHistonesHL-60 CellsHumansImmunoblottingImmunoglobulin GLupus Erythematosus, SystemicMiceAutoantibodiesAutoantigensChromatinHistonesImmunoglobulin G

Identifiers

PMID22300536
PMCPMC3392818
OpenAlexW2148020555

What OpenQuestion holds

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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 OpenQuestion graph.