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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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.
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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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