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Using the circulating proteome to assess type I interferon activity in systemic lupus erythematosus
Type I interferon (IFN) drives pathology in systemic lupus erythematosus (SLE) and can be tracked via IFN-inducible transcripts in blood. Here, we examined whether measurement of circulating proteins, which enter the bloodstream from inflamed tissues, also offers insight into global IFN activity. Us...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064569/ https://www.ncbi.nlm.nih.gov/pubmed/32157125 http://dx.doi.org/10.1038/s41598-020-60563-9 |
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author | Smith, Michael A. Chiang, Chia-Chien Zerrouki, Kamelia Rahman, Saifur White, Wendy I. Streicher, Katie Rees, William A. Schiffenbauer, Adam Rider, Lisa G. Miller, Frederick W. Manna, Zerai Hasni, Sarfaraz Kaplan, Mariana J. Siegel, Richard Sinibaldi, Dominic Sanjuan, Miguel A. Casey, Kerry A. |
author_facet | Smith, Michael A. Chiang, Chia-Chien Zerrouki, Kamelia Rahman, Saifur White, Wendy I. Streicher, Katie Rees, William A. Schiffenbauer, Adam Rider, Lisa G. Miller, Frederick W. Manna, Zerai Hasni, Sarfaraz Kaplan, Mariana J. Siegel, Richard Sinibaldi, Dominic Sanjuan, Miguel A. Casey, Kerry A. |
author_sort | Smith, Michael A. |
collection | PubMed |
description | Type I interferon (IFN) drives pathology in systemic lupus erythematosus (SLE) and can be tracked via IFN-inducible transcripts in blood. Here, we examined whether measurement of circulating proteins, which enter the bloodstream from inflamed tissues, also offers insight into global IFN activity. Using a novel protocol we generated 1,132 aptamer-based protein measurements from anti-dsDNA(pos) SLE blood samples and derived an IFN protein signature (IFNPS) that approximates the IFN 21-gene signature (IFNGS). Of 82 patients with SLE, IFNPS was elevated for 89% of IFNGS-high patients (49/55) and 26% of IFNGS-low patients (7/27). IFNGS-high/IFNPS-high patients exhibited activated NK, CD4, and CD8 T cells, while IFNPS-high only patients did not. IFNPS correlated with global disease activity in lymphopenic and non-lymphopenic patients and decreased following type I IFN neutralisation with anifrolumab in the SLE phase IIb study, MUSE. In summary, we developed a protein signature that reflects IFNGS and identifies a new subset of patients with SLE who have IFN activity. |
format | Online Article Text |
id | pubmed-7064569 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-70645692020-03-18 Using the circulating proteome to assess type I interferon activity in systemic lupus erythematosus Smith, Michael A. Chiang, Chia-Chien Zerrouki, Kamelia Rahman, Saifur White, Wendy I. Streicher, Katie Rees, William A. Schiffenbauer, Adam Rider, Lisa G. Miller, Frederick W. Manna, Zerai Hasni, Sarfaraz Kaplan, Mariana J. Siegel, Richard Sinibaldi, Dominic Sanjuan, Miguel A. Casey, Kerry A. Sci Rep Article Type I interferon (IFN) drives pathology in systemic lupus erythematosus (SLE) and can be tracked via IFN-inducible transcripts in blood. Here, we examined whether measurement of circulating proteins, which enter the bloodstream from inflamed tissues, also offers insight into global IFN activity. Using a novel protocol we generated 1,132 aptamer-based protein measurements from anti-dsDNA(pos) SLE blood samples and derived an IFN protein signature (IFNPS) that approximates the IFN 21-gene signature (IFNGS). Of 82 patients with SLE, IFNPS was elevated for 89% of IFNGS-high patients (49/55) and 26% of IFNGS-low patients (7/27). IFNGS-high/IFNPS-high patients exhibited activated NK, CD4, and CD8 T cells, while IFNPS-high only patients did not. IFNPS correlated with global disease activity in lymphopenic and non-lymphopenic patients and decreased following type I IFN neutralisation with anifrolumab in the SLE phase IIb study, MUSE. In summary, we developed a protein signature that reflects IFNGS and identifies a new subset of patients with SLE who have IFN activity. Nature Publishing Group UK 2020-03-10 /pmc/articles/PMC7064569/ /pubmed/32157125 http://dx.doi.org/10.1038/s41598-020-60563-9 Text en © The Author(s) 2020 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. 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/. |
spellingShingle | Article Smith, Michael A. Chiang, Chia-Chien Zerrouki, Kamelia Rahman, Saifur White, Wendy I. Streicher, Katie Rees, William A. Schiffenbauer, Adam Rider, Lisa G. Miller, Frederick W. Manna, Zerai Hasni, Sarfaraz Kaplan, Mariana J. Siegel, Richard Sinibaldi, Dominic Sanjuan, Miguel A. Casey, Kerry A. Using the circulating proteome to assess type I interferon activity in systemic lupus erythematosus |
title | Using the circulating proteome to assess type I interferon activity in systemic lupus erythematosus |
title_full | Using the circulating proteome to assess type I interferon activity in systemic lupus erythematosus |
title_fullStr | Using the circulating proteome to assess type I interferon activity in systemic lupus erythematosus |
title_full_unstemmed | Using the circulating proteome to assess type I interferon activity in systemic lupus erythematosus |
title_short | Using the circulating proteome to assess type I interferon activity in systemic lupus erythematosus |
title_sort | using the circulating proteome to assess type i interferon activity in systemic lupus erythematosus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064569/ https://www.ncbi.nlm.nih.gov/pubmed/32157125 http://dx.doi.org/10.1038/s41598-020-60563-9 |
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