El-Sherbiny, YM orcid.org/0000-0003-4791-3475, Psarras, A, Md Yusof, M et al. (8 more authors) (2018) A novel two-score system for interferon status segregates autoimmune diseases and correlates with clinical features. Scientific Reports, 8. 5793. ISSN 2045-2322
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 affected by the modularity of the ISG transcriptome, cell-specific 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 IFN-subtypes and both scores varied between cell subsets. IFN-Score-A differentiated Systemic Lupus Erythematosus (SLE) from both Rheumatoid Arthritis (RA) and Healthy Controls (HC) (both p<0.001), while IFN-Score-B differentiated 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) classification, significant differences 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 classification of IFN status. This system should allow improvement in diagnosis, stratification, and therapy in IFN-mediated autoimmunity.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2018. 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. The 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/. |
Keywords: | Molecular medicine; Systemic lupus erythematosus |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) |
Funding Information: | Funder Grant number Astra Zeneca D2287C00002 |
Depositing User: | Symplectic Publications |
Date Deposited: | 11 Apr 2018 10:42 |
Last Modified: | 11 Apr 2018 10:44 |
Status: | Published |
Publisher: | Nature Publishing Group |
Identification Number: | 10.1038/s41598-018-24198-1 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:129357 |
Commentary/Response Threads
- El-Sherbiny, YM, Psarras, A, Md Yusof, M, Hensor, E, Tooze, R, Doody, G, Mohamed, A, McGonagle, D, Wittmann, M, Emery, P and Vital, E A novel two-score system for interferon status segregates autoimmune diseases and correlates with clinical features. (deposited 11 Apr 2018 10:42) [Currently Displayed]