Transcriptomics

Dataset Information

52

Transcriptional profiling of the tuberculin skin test in healthy volunteers and in rheumatoid arthritis patients treated with methotrexate or anti-TNF therapy


ABSTRACT: Anti-TNF therapy has transformed the management of rheumatoid arthritis (RA); however little is known about its effects on cell mediated immune responses and TNF-inducible activity at the site of inflammation. Here, we used the tuberculin skin test (TST) as a standardised in vivo human challenge model to make systems level assessments of the effects of anti-TNF therapy in a prototypic cell mediated immune response. RA patients (treated with monoclonal anti-TNF antibodies (adalimumab or infliximab), the soluble TNF receptor etanercept or the standard therapy methotrexate) and healthy volunteers with immunological memory to Mycobacterium tuberculosis antigens were identified using an interferon-γ release assay of peripheral blood. Two units tuberculin or an equivalent volume of saline was injected into the forearm of study participants (n=50). After 72 hours, 3 mm skin punch biopsies were taken from the injection site and processed for whole genome transcriptional profiling by Agilent gene microarray.

ORGANISM(S): Homo sapiens  

SUBMITTER: Carolin Turner  

PROVIDER: E-MTAB-5093 | ArrayExpress | 2017-08-04

REPOSITORIES: ArrayExpress

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Publications

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.

Byng-Maddick Rachel R   Turner Carolin T CT   Pollara Gabriele G   Ellis Matthew M   Guppy Naomi J NJ   Bell Lucy C K LCK   Ehrenstein Michael R MR   Noursadeghi Mahdad M  

Frontiers in immunology 20170804


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,  ...[more]

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