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The interferon gene signature as a clinically relevant biomarker in autoimmune rheumatic disease

Lookup NU author(s): Dr Faye Cooles, Professor John IsaacsORCiD

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Abstract

© 2021 Elsevier LtdThe interferon gene signature (IGS) is derived from the expression of interferon-regulated genes and is classically increased in response to type I interferon exposure. A raised whole blood IGS has increasingly been reported in rheumatic diseases as sequencing technology has advanced. Although its role remains unclear, we explore how a raised IGS can function as a clinically relevant biomarker, independent of whether it is a bystander effect or a key pathological process. For example, a raised IGS can act as a diagnostic biomarker when predicting rheumatoid arthritis in patients with arthralgia and anti-citrullinated protein antibodies, or predicting systemic lupus erythematous (SLE) in those with antinuclear antibodies; a theragnostic biomarker when predicting response for patients receiving disease modifying therapy, such as rituximab in rheumatoid arthritis; a biomarker of disease activity (early rheumatoid arthritis, dermatomyositis, systemic sclerosis, SLE); or finally a predictor of clinical characteristics, such as lupus nephritis in SLE or disease burden in primary Sjögren's syndrome. A high IGS does not uniformly predict worse clinical phenotypes across all diseases, as demonstrated by a reduced disease burden in primary Sjögren's syndrome, nor does it predict a universally poorer response to all therapies, as shown in rheumatoid arthritis. This dichotomy highlights both the complexity of type I interferon signalling in vivo and the current lack of standardisation when calculating the IGS. The IGS as a biomarker warrants further exploration, with beneficial clinical applications anticipated in multiple rheumatic diseases.


Publication metadata

Author(s): Cooles FAH, Isaacs JD

Publication type: Review

Publication status: Published

Journal: The Lancet Rheumatology

Year: 2022

Volume: 4

Issue: 1

Pages: e61-e72

Print publication date: 01/01/2022

Online publication date: 17/11/2021

Acceptance date: 02/04/2020

ISSN (electronic): 2665-9913

Publisher: Elsevier Ltd

URL: https://doi.org/10.1016/S2665-9913(21)00254-X

DOI: 10.1016/S2665-9913(21)00254-X


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