Evidence map›Paper›PMID 25893403›Full record

ArticlePloS one2015

Differential Cytokine Changes in Patients with Myasthenia Gravis with Antibodies against AChR and MuSK.

Vuslat Yilmaz, Piraye Oflazer, Fikret Aysal, Hacer Durmus, Kostas Poulas, Sibel P Yentur, Yesim Gulsen-Parman, Socrates Tzartos, Alexander Marx, Erdem Tuzun and 2 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 8% 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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.

  1. Pooled it
  2. Circulating inflammatory proteins as pathogenic mediators and potential therapeutic targets in myasthenia gravis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Antibody Therapies in Autoimmune Neuromuscular Junction Disorders: Approach to Myasthenic Crisis and Chronic Management.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022
    Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Immunological markers andBiomedical reports · 2020
    Article
  17. CD4Frontiers in immunology · 2020
    Article
  18. Review
  19. Article
  20. 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

12 authors at 5 institutions in 4 countries.

Vuslat YilmazDepartment of Physiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Piraye OflazerDepartment of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Fikret AysalDepartment of Neurology, Bakirkoy Research and Training Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey.
Hacer DurmusDepartment of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Kostas PoulasDepartment of Pharmacy, School of Health Sciences, University of Patras, Patras, Greece.
Sibel P YenturDepartment of Physiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Yesim Gulsen-ParmanDepartment of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Socrates TzartosHellenic Pasteur Institute, Athens, Greece.
Alexander MarxInstitute of Pathology, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany.
Erdem TuzunDepartment of Neuroscience, Institute for Experimental Medical Research, University of Istanbul, Istanbul, Turkey.
Feza DeymeerDepartment of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Güher Saruhan-DireskeneliDepartment of Physiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Istanbul University · TRBakırköy Psychiatric Hospital · TRPasteur Hellenic Institute · GRUniversity Medical Centre Mannheim · DEUniversity of Patras · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neuromuscular transmission failure in myasthenia gravis (MG) is most commonly elicited by autoantibodies (ab) to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th) 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in patients with AChR-MG, MuSK-MG and healthy controls (CON). Peripheral blood mononuclear cells (PBMC) were activated in vitro by anti-CD3, and cytokines were quantified in supernatants. In purified blood CD4+ T cells, RNA of various cytokines, Th subtype specific transcription factors and the co-stimulatory molecule, CD40L, were quantified by qRT-PCR. Plasma levels of Th1, Th2 and Th17 related cytokines were overall not significantly different between MG subtypes and CON. By contrast, in vitro stimulated PBMC from MuSK-MG but not AChR-MG patients showed significantly increased secretion of the Th1, Th17 and T follicular helper cell related cytokines, IFN-γ, IL-17A and IL-21. Stimulated expression of IL-4, IL-6, IL-10 and IL-13 was not significantly different. At the RNA level, expression of CD40L by CD4+ T cells was reduced in both AChR-MG and MuSK-MG patients while expression of Th subset related cytokines and transcription factors were normal. Immunosuppression treatment had two effects: First, it reduced levels of IL12p40 in the plasma of AChR-MG and MuSK-MG patients, leaving other cytokine levels unchanged; second, it reduced spontaneous secretion of IFN-γ and increased secretion of IL-6 and IL-10 by cultured PBMC from AChR-MG, but not MuSK-MG patients. We conclude that Th1 and Th17 immune reactions play a role in MuSK-MG. Immunosuppression attenuates the Th1 response in AChR-MG and MuSK-MG, but otherwise modulates immune responses in AChR-MG and MuSK-MG patients differentially.

Indexed as

AdultAutoantibodiesCD3 ComplexCD40 LigandCD4-Positive T-LymphocytesCell SeparationCytokinesDemographyFemaleHumansImmunosuppression TherapyInterleukin-12 Subunit p40Leukocytes, MononuclearMaleMyasthenia GravisReceptor Protein-Tyrosine KinasesAutoantibodiesCD3 ComplexCD40 LigandCytokinesInterleukin-12 Subunit p40MUSK protein, humanReceptor Protein-Tyrosine KinasesReceptors, CholinergicRNA, Messenger

Identifiers

PMID25893403
PMCPMC4403992
OpenAlexW2032858097

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.