Byng-Maddick, R;
Turner, CT;
Pollara, G;
Ellis, M;
Guppy, NJ;
Bell, LCK;
Ehrenstein, MR;
(2017)
Tumor necrosis Factor (TNF) Bioactivity at the site of an acute cell-Mediated immune response is Preserved in rheumatoid arthritis Patients responding to anti-TNF Therapy.
Frontiers in Immunology
, 8
, Article 932. 10.3389/fimmu.2017.00932.
Preview |
Text (Published article)
Byng_Tumor_necrosis_Factor (TNF).pdf - Published Version Download (3MB) | Preview |
![[thumbnail of Supplementary data sheet 1]](https://discovery.ucl.ac.uk/style/images/fileicons/other.png) |
Spreadsheet (Supplementary data sheet 1)
Byng_Tumor_necrosis_Factor (TNF)_S1.xlsx Download (18kB) |
|
Spreadsheet (Supplementary data sheet 2)
Byng_Tumor_necrosis_Factor (TNF)_S2.xlsx Download (204kB) |
|
Spreadsheet (Supplementary data sheet 3)
Byng_Tumor_necrosis_Factor (TNF)_S3.xlsx Download (23kB) |
|
Spreadsheet (Supplementary data sheet 4)
Byng_Tumor_necrosis_Factor (TNF)_S4.xlsx Download (85kB) |
Abstract
The impact of anti-tumor necrosis factor (TNF) therapies on inducible TNF-dependent activity in humans has never been evaluated in vivo. We aimed to test the hypothesis that patients responding to anti-TNF treatments exhibit attenuated TNF-dependent immune responses at the site of an immune challenge. We developed and validated four context-specific TNF-inducible transcriptional signatures to quantify TNF bioactivity in transcriptomic data. In anti-TNF treated rheumatoid arthritis (RA) patients, we measured the expression of these biosignatures in blood, and in skin biopsies from the site of tuberculin skin tests (TSTs) as a human experimental model of multivariate cell-mediated immune responses. In blood, anti-TNF therapies attenuated TNF bioactivity following ex vivo stimulation. However, at the site of the TST, TNF-inducible gene expression and genome-wide transcriptional changes associated with cell-mediated immune responses were comparable to that of RA patients receiving methotrexate only. These data demonstrate that anti-TNF agents in RA patients do not inhibit inducible TNF activity at the site of an acute inflammatory challenge in vivo, as modeled by the TST. We hypothesize instead that their therapeutic effects are limited to regulating TNF activity in chronic inflammation or by alternative non-canonical pathways.
| Type: | Article |
|---|---|
| Title: | Tumor necrosis Factor (TNF) Bioactivity at the site of an acute cell-Mediated immune response is Preserved in rheumatoid arthritis Patients responding to anti-TNF Therapy |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2017.00932 |
| Publisher version: | https://doi.org/10.3389/fimmu.2017.00932 |
| Language: | English |
| Additional information: | Copyright © 2017 Byng-Maddick, Turner, Pollara, Ellis, Guppy, Bell, Ehrenstein and Noursadeghi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | tumor necrosis factor, anti-tumor necrosis factor, rheumatoid arthritis, tuberculin skin test, transcriptional profiling |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1571639 |
Archive Staff Only
 |
View Item |
