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In vitro response pattern of monocytes after tmTNF reverse signaling predicts response to anti-TNF therapy in rheumatoid arthritis

Overview of attention for article published in Journal of Translational Medicine, August 2015
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Title
In vitro response pattern of monocytes after tmTNF reverse signaling predicts response to anti-TNF therapy in rheumatoid arthritis
Published in
Journal of Translational Medicine, August 2015
DOI 10.1186/s12967-015-0620-z
Pubmed ID
Authors

Undine Meusch, Marco Krasselt, Manuela Rossol, Christoph Baerwald, Maria Klingner, Ulf Wagner

Abstract

Treatment with TNF inhibitors is very efficient in the majority of the patients with rheumatoid arthritis (RA), but it does not achieve a sufficient treatment response in 40-50% of the cases. Goal of the study was to assess functional ex vivo-tests of RA monocytes as prognostic parameters of the subsequent treatment response. 20 anti-TNF naïve RA patients were enrolled in a prospective, open-label trial, and Etanercept therapy was initiated. Prior to treatment, reverse signaling was induced in peripheral blood monocytes by tmTNF crosslinking via TNFR2:Ig construct Etanercept in a standardized ex vivo-assay. Released cytokine and cytokine receptor concentrations were determined as parameters of the monocyte response. Crosslinking of tmTNF and consecutive reverse signaling led to production of pro- and anti-inflammatory cytokines and of soluble cytokine decoy receptors such as sTNFR1 and sIL-1R2. Several of the measured concentrations were found to correlate with the treatment response according to the EULAR criteria. The correlation was most pronounced in sTNFR1 concentrations (r = -0.657, p = 0.0031), which also predicted a good clinical response with the highest sensitivity and specificity according to EULAR criteria. Herein we propose that the tmTNF crosslinking-triggered shedding of soluble decoy receptors and production of anti-inflammatory cytokines could contribute to the clinical efficacy of TNF inhibitors, and that in vitro quantification of this secretion by RA monocytes prior to treatment can be used to predict the clinical response. Further development of such standardized tests could be a step towards personalized medicine by providing rheumatologists with a rational choice for first line biological therapy in patients with RA.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Portugal 1 4%
Unknown 27 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 21%
Student > Ph. D. Student 5 18%
Student > Master 4 14%
Unspecified 4 14%
Student > Postgraduate 4 14%
Other 5 18%
Readers by discipline Count As %
Medicine and Dentistry 8 29%
Immunology and Microbiology 6 21%
Agricultural and Biological Sciences 5 18%
Unspecified 5 18%
Biochemistry, Genetics and Molecular Biology 2 7%
Other 2 7%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 06 August 2015.
All research outputs
#2,896,567
of 5,450,695 outputs
Outputs from Journal of Translational Medicine
#848
of 1,535 outputs
Outputs of similar age
#103,617
of 190,069 outputs
Outputs of similar age from Journal of Translational Medicine
#90
of 108 outputs
Altmetric has tracked 5,450,695 research outputs across all sources so far. This one is in the 33rd percentile – i.e., 33% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,535 research outputs from this source. They receive a mean Attention Score of 4.1. This one is in the 14th percentile – i.e., 14% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 190,069 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 108 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.