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Arthritis Research & Therapy

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01-12-2021 | Etanercept | Research article

Differential impacts of TNFα inhibitors on the transcriptome of Th cells

Authors: Ching-Huang Ho, Andrea A. Silva, Beverly Tomita, Hui-Ying Weng, I-Cheng Ho

Published in: Arthritis Research & Therapy | Issue 1/2021

Abstract

Background

Targeting TNFα is beneficial in many autoimmune and inflammatory diseases, including rheumatoid arthritis. However, the response to each of the existing TNFα inhibitors (TNFis) can be patient- and/or disease-dependent. In addition, TNFis can induce the production of type 1 interferons (IFNs), which contribute to their non-infection side effects, such as pustular psoriasis. Thus far, the molecular mechanisms mediating the drug-specific effects of TNFis and their induction of type 1 IFNs are not fully understood.

Methods

Peripheral blood mononuclear cells (PBMCs) were collected from healthy donors and stimulated in vitro with anti-CD3 and anti-CD28 in the absence or presence of adalimumab, etanercept, or certolizumab. Th cells were isolated from the stimulated PBMCs, and their RNA was subjected to RNA-seq and quantitative polymerase chain reaction.

Results

Adalimumab and etanercept, which contain Fc, but not certolizumab, which does not contain Fc, inhibited the expression of several effector cytokines by Th cells within anti-CD3/anti-CD28-stimulated PBMCs. Transcriptomic analyses further showed that adalimumab, but not certolizumab, reciprocally induced type 1 IFN signals and the expression of CD96 and SIRPG in Th cells. The unique effects of adalimumab were not due to preferential neutralization of soluble TNFα but instead were mediated by several distinct mechanisms independent or dependent of Fc-facilitated physical interaction between Th cells and CD14+ monocytes.

Conclusions

TNFis can have drug-specific effects on the transcriptional profile of Th cells.

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Title: Differential impacts of TNFα inhibitors on the transcriptome of Th cells
Authors: Ching-Huang Ho
Andrea A. Silva
Beverly Tomita
Hui-Ying Weng
I-Cheng Ho
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Etanercept
Certolizumab
Adalimumab
Cytokines
Interferon
Anti-CD3 Antibody
Published in: Arthritis Research & Therapy / Issue 1/2021
Electronic ISSN: 1478-6362
DOI: https://doi.org/10.1186/s13075-021-02558-z

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