Evidence map›Paper›PMID 27368295›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016

Epigenetic changes in T-cell and monocyte signatures and production of neurotoxic cytokines in ALS patients.

Larry Lam, Lydia Chin, Ramesh C Halder, Bien Sagong, Sam Famenini, James Sayre, Dennis Montoya, Liudmilla Rubbi, Matteo Pellegrini, Milan Fiala

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

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 5% 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

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Epigenetics in Neurodegenerative Diseases.Sub-cellular biochemistry · 2025
    Review
  6. Review
  7. Eomesodermin expression in CD4CNS neuroscience & therapeutics · 2024
    Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Human DNA methylation signatures differentiate persistent from resolving MRSA bacteremia.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
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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

10 authors at 1 institution in 1 country.

Larry LamDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, California, USA.
Lydia ChinDepartment of Surgery, UCLA School of Medicine, University of California, Los Angeles, Los Angeles, California, USA; and.
Ramesh C HalderDepartment of Surgery, UCLA School of Medicine, University of California, Los Angeles, Los Angeles, California, USA; and.
Bien SagongDepartment of Surgery, UCLA School of Medicine, University of California, Los Angeles, Los Angeles, California, USA; and.
Sam FameniniDepartment of Surgery, UCLA School of Medicine, University of California, Los Angeles, Los Angeles, California, USA; and.
James SayreDepartment of Biostatistics, UCLA School of Public Health, University of California, Los Angeles, Los Angeles, California, USA.
Dennis MontoyaDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, California, USA.
Liudmilla RubbiDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, California, USA.
Matteo PellegriniDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, California, USA.
Milan FialaDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, California, USA; Department of Surgery, UCLA School of Medicine, University of California, Los Angeles, Los Angeles, California, USA; and fiala@mednet.ucla.edu.
University of California, Los Angeles · US

Funding

Vitamin D Metabolism in LeprosyP50AR063020 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MODLIN, ROBERT L · 2012 to 2016
$7.8M
TRAINING PROGRAM IN CELLULAR AND MOLECULAR BIOLOGYT32GM008553 · NIGMS · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI MLODZIK, MAREK · 1995 to 2012
$1.6M
NIAMS NIH HHS P50 AR063020NIGMS NIH HHS T32 GM008553
6 · The paper itself

Abstract

We have investigated transcriptional and epigenetic differences in peripheral blood mononuclear cells (PBMCs) of monozygotic female twins discordant in the diagnosis of amyotrophic lateral sclerosis (ALS). Exploring DNA methylation differences by reduced representation bisulfite sequencing (RRBS), we determined that, over time, the ALS twin developed higher abundances of the CD14 macrophages and lower abundances of T cells compared to the non-ALS twin. Higher macrophage signature in the ALS twin was also shown by RNA sequencing (RNA-seq). Moreover, the twins differed in the methylome at loci near several genes, including EGFR and TNFRSF11A, and in the pathways related to the tretinoin and H3K27me3 markers. We also tested cytokine production by PBMCs. The ALS twin's PBMCs spontaneously produced IL-6 and TNF-α, whereas PBMCs of the healthy twin produced these cytokines only when stimulated by superoxide dismutase (SOD)-1. These results and flow cytometric detection of CD45 and CD127 suggest the presence of memory T cells in both twins, but effector T cells only in the ALS twin. The ALS twin's PBMC supernatants, but not the healthy twin's, were toxic to rat cortical neurons, and this toxicity was strongly inhibited by an IL-6 receptor antibody (tocilizumab) and less well by TNF-α and IL-1β antibodies. The putative neurotoxicity of IL-6 and TNF-α is in agreement with a high expression of these cytokines on infiltrating macrophages in the ALS spinal cord. We hypothesize that higher macrophage abundance and increased neurotoxic cytokines have a fundamental role in the phenotype and treatment of certain individuals with ALS.-Lam, L., Chin, L., Halder, R. C., Sagong, B., Famenini, S., Sayre, J., Montoya, D., Rubbi L., Pellegrini, M., Fiala, M. Epigenetic changes in T-cell and monocyte signatures and production of neurotoxic cytokines in ALS patients.

Indexed as

Epigenesis, GeneticAgedAmyotrophic Lateral SclerosisAnimalsCytokinesFemaleHumansLeukocytes, MononuclearMacrophagesMaleMiddle AgedMonocytesNeuronsRatsSpinal CordT-LymphocytesCytokinesTumor Necrosis Factor-alphaALSinflammationSOD-1

Identifiers

PMID27368295
PMCPMC5024692
OpenAlexW2471056538

What OpenQuestion holds

Textmetadata
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.