Single-cell landscape of peripheral immune response in patients with anti-melanoma differentiation-associated gene 5 dermatomyositis
© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissionsoup.com..
OBJECTIVE: Anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM) is a rare but life-threatening autoimmune disorder with a high risk to develop rapidly progressive interstitial lung disease. Current empirical therapies have limited improvement on patients' survival, as little is known about the aetiology of MDA5 DM. To best understand its immune landscape, we applied single-cell RNA sequencing (scRNA-seq) to peripheral blood samples from DM patients and healthy controls.
METHODS: Peripheral blood mononuclear cells (PBMCs) from eight DM patients, comprising three distinct subtypes, as well as two healthy donors, were sequenced by 10X Genomics platform. Additional scRNA-seq data of four healthy donors were incorporated for further bioinformatic analysis.
RESULTS: Aberrant increased proportions of CD14+ monocyte and plasma cells were observed in MDA5 DM samples. Moreover, we found overactivated type I interferon response and antiviral immunity in both innate and adaptive immune cells derived from MDA5 DM patients, which was positively correlated with disease severity. Importantly, a unique subset of CD14+ monocyte that highly expressed interferon alpha-inducible protein 27 (IFI27, a biomarker for viral infection) and interferon induced with helicase C domain 1 (IFIH1, encodes MDA5) was specifically identified in MDA5 DM samples for the first time.
CONCLUSION: Our study demonstrates the peripheral immune cell atlas of different DM subtypes, provides compelling evidence for viral infection-derived origin of MDA5 DM, and offers potential targets for innovative therapeutic interventions.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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| Enthalten in: |
Rheumatology (Oxford, England) - (2023) vom: 06. Nov. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
He, Jiangping [VerfasserIn] |
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| Links: |
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| Themen: |
Antiviral immunity |
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| Anmerkungen: |
Date Revised 09.11.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1093/rheumatology/kead597 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364331976 |
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| 245 | 1 | 0 | |a Single-cell landscape of peripheral immune response in patients with anti-melanoma differentiation-associated gene 5 dermatomyositis |
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| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissionsoup.com. | ||
| 520 | |a OBJECTIVE: Anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM) is a rare but life-threatening autoimmune disorder with a high risk to develop rapidly progressive interstitial lung disease. Current empirical therapies have limited improvement on patients' survival, as little is known about the aetiology of MDA5 DM. To best understand its immune landscape, we applied single-cell RNA sequencing (scRNA-seq) to peripheral blood samples from DM patients and healthy controls | ||
| 520 | |a METHODS: Peripheral blood mononuclear cells (PBMCs) from eight DM patients, comprising three distinct subtypes, as well as two healthy donors, were sequenced by 10X Genomics platform. Additional scRNA-seq data of four healthy donors were incorporated for further bioinformatic analysis | ||
| 520 | |a RESULTS: Aberrant increased proportions of CD14+ monocyte and plasma cells were observed in MDA5 DM samples. Moreover, we found overactivated type I interferon response and antiviral immunity in both innate and adaptive immune cells derived from MDA5 DM patients, which was positively correlated with disease severity. Importantly, a unique subset of CD14+ monocyte that highly expressed interferon alpha-inducible protein 27 (IFI27, a biomarker for viral infection) and interferon induced with helicase C domain 1 (IFIH1, encodes MDA5) was specifically identified in MDA5 DM samples for the first time | ||
| 520 | |a CONCLUSION: Our study demonstrates the peripheral immune cell atlas of different DM subtypes, provides compelling evidence for viral infection-derived origin of MDA5 DM, and offers potential targets for innovative therapeutic interventions | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a IFI27 | |
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| 650 | 4 | |a dermatomyositis | |
| 650 | 4 | |a interferon | |
| 650 | 4 | |a single-cell RNA sequencing | |
| 700 | 1 | |a Liu, Zhicheng |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiaofang |e verfasserin |4 aut | |
| 700 | 1 | |a Yi, Caihong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yanzi |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Zhenyang |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Quan |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Jiao |e verfasserin |4 aut | |
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