A novel two-score system for interferon status segregates autoimmune diseases and correlates with clinical features

El-Sherbiny, YM ORCID: https://orcid.org/0000-0003-4791-3475, Psarras, A, Md Yusof, MY, Hensor, EMA, Tooze, R, Doody, G, Mohamed, AAA, McGonagle, D, Wittmann, M, Emery, P and Vital, EM, 2018. A novel two-score system for interferon status segregates autoimmune diseases and correlates with clinical features. Scientific Reports, 8: 5793. ISSN 2045-2322

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Abstract

Measurement of type I interferon (IFN-I) has potential to diagnose and stratify autoimmune diseases, but existing results have been inconsistent. Interferon-stimulated-gene (ISG) based methods may be afected by the modularity of the ISG transcriptome, cell-specifc expression, response to IFN-subtypes and bimodality of expression. We developed and clinically validated a 2-score system (IFN-Score-A and -B) using Factor Analysis of 31 ISGs measured by TaqMan selected from 3-IFN-annotated modules. We evaluated these scores using in-vitro IFN stimulation as well as in sorted cells then clinically validated in a cohort of 328 autoimmune disease patients and healthy controls. ISGs varied in response to IFNsubtypes and both scores varied between cell subsets. IFN-Score-A diferentiated Systemic Lupus Erythematosus (SLE) from both Rheumatoid Arthritis (RA) and Healthy Controls (HC) (both p<0.001), while IFN-Score-B diferentiated SLE and RA from HC (both p<0.001). In SLE, both scores were associated with cutaneous and hematological (all p<0.05) but not musculoskeletal disease activity. Comparing with bimodal (IFN-high/low) classifcation, signifcant diferences in IFN-scores were found between diagnostic groups within the IFN-high group. Our continuous 2-score system is more clinically relevant than a simple bimodal classifcation of IFN status. This system should allow improvement in diagnosis, stratifcation, and therapy in IFN-mediated autoimmunity.

Item Type:	Journal article
Publication Title:	Scientific Reports
Creators:	El-Sherbiny, Y.M., Psarras, A., Md Yusof, M.Y., Hensor, E.M.A., Tooze, R., Doody, G., Mohamed, A.A.A., McGonagle, D., Wittmann, M., Emery, P. and Vital, E.M.
Publisher:	Nature Publishing Group
Date:	11 April 2018
Volume:	8
ISSN:	2045-2322
Identifiers:	Number Type 10.1038/s41598-018-24198-1 DOI 24198 Publisher Item Identifier
Rights:	© The Author(s) 2018. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Divisions:	Schools > School of Science and Technology
Record created by:	Jill Tomkinson
Date Added:	06 Feb 2019 14:02
Last Modified:	06 Feb 2019 14:02
URI:	https://irep.ntu.ac.uk/id/eprint/35772

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