Evidence map›Paper›PMID 26401511›Full record

ArticleAnnals of clinical and translational neurology2015

cFLIP overexpression in T cells in thymoma-associated myasthenia gravis.

Djeda Belharazem, Berthold Schalke, Ralf Gold, Wilfred Nix, Mario Vitacolonna, Peter Hohenberger, Eric Roessner, Torsten J Schulze, Güher Saruhan-Direskeneli, Vuslat Yilmaz and 3 more

Open access · goldAbstract read
In one paragraph

Article in Annals of clinical and translational neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.4field-weighted citation impact, top 34% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

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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

13 authors at 7 institutions in 2 countries.

Djeda BelharazemInstitute of Pathology, University Medical Centre Mannheim, University of Heidelberg Mannheim, Germany.
Berthold SchalkeDepartment of Neurology, University of Regensburg Regensburg, Germany.
Ralf GoldDepartment of Neurology, University of Bochum Bochum, Germany.
Wilfred NixDepartment of Neurology, University of Mainz Mainz, Germany.
Mario VitacolonnaDepartment of Thoracic Surgery, University Medical Centre Mannheim Mannheim, Germany.
Peter HohenbergerDepartment of Thoracic Surgery, University Medical Centre Mannheim Mannheim, Germany.
Eric RoessnerDepartment of Thoracic Surgery, University Medical Centre Mannheim Mannheim, Germany.
Torsten J SchulzeInstitute for Transfusion Medicine and Immunology, German Red Cross Blood Service, University Medical Centre Mannheim Mannheim, Germany.
Güher Saruhan-DireskeneliDepartment of Physiology, School of Medicine, Istanbul University Istanbul, Turkey.
Vuslat YilmazDepartment of Physiology, School of Medicine, Istanbul University Istanbul, Turkey.
German OttDepartment of Pathology, Robert-Bosch Hospital Stuttgart, Germany.
Philipp StröbelInstitute of Pathology, University of Goettingen Goettingen, Germany.
Alexander MarxInstitute of Pathology, University Medical Centre Mannheim, University of Heidelberg Mannheim, Germany.
University Medical Centre Mannheim · DEHeidelberg University · DEIstanbul University · TRJohannes Gutenberg University Mainz · DERobert Bosch Hospital · DEUniversity of Göttingen · DEUniversity of Regensburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThe capacity of thymomas to generate mature CD4+ effector T cells from immature precursors inside the tumor and export them to the blood is associated with thymoma-associated myasthenia gravis (TAMG). Why TAMG(+) thymomas generate and export more mature CD4+ T cells than MG(-) thymomas is unknown.

methodsUnfixed thymoma tissue, thymocytes derived thereof, peripheral blood mononuclear cells (PBMCs), T-cell subsets and B cells were analysed using qRT-PCR and western blotting. Survival of PBMCs was measured by MTT assay. FAS-mediated apoptosis in PBMCs was quantified by flow cytometry. NF-κB in PBMCs was inhibited by the NF-κB-Inhibitor, EF24 prior to FAS-Ligand (FASLG) treatment for apoptosis induction.

resultsExpression levels of the apoptosis inhibitor cellular FLICE-like inhibitory protein (c-FLIP) in blood T cells and intratumorous thymocytes were higher in TAMG(+) than in MG(-) thymomas and non-neoplastic thymic remnants. Thymocytes and PBMCs of TAMG patients showed nuclear NF-κB accumulation and apoptosis resistance to FASLG stimulation that was sensitive to NF-κB blockade. Thymoma removal reduced cFLIP expression in PBMCs.

interpretationWe conclude that thymomas induce cFLIP overexpression in thymocytes and their progeny, blood T cells. We suggest that the stronger cFLIP overexpression in TAMG(+) compared to MG(-) thymomas allows for the more efficient generation of mature CD4+ T cells in TAMG(+) thymomas. cFLIP overexpression in thymocytes and exported CD4+ T cells of patients with TAMG might contribute to the pathogenesis of TAMG by impairing central and peripheral T-cell tolerance.

Identifiers

PMID26401511
PMCPMC4574807
OpenAlexW1899309971

What OpenQuestion holds

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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.