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Single-cell profiling reveals distinct adaptive immune hallmarks in MDA5+ dermatomyositis with therapeutic implications
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Single-cell profiling reveals distinct adaptive immune hallmarks in MDA5+ dermatomyositis with therapeutic implications
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Journal Article
Single-cell profiling reveals distinct adaptive immune hallmarks in MDA5+ dermatomyositis with therapeutic implications
2022
Overview
Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5
+
DM) is an autoimmune condition associated with rapidly progressive interstitial lung disease and high mortality. The aetiology and pathogenesis of MDA5
+
DM are still largely unknown. Here we describe the immune signatures of MDA5
+
DM via single-cell RNA sequencing, flow cytometry and multiplex immunohistochemistry in peripheral B and T cells and in affected lung tissue samples from one patient. We find strong peripheral antibody-secreting cell and CD8
+
T cell responses as cellular immune hallmarks, and over-stimulated type I interferon signaling and associated metabolic reprogramming as molecular immune signature in MDA5
+
DM. High frequency of circulating ISG15
+
CD8
+
T cells at baseline predicts poor one-year survival in MDA5
+
DM patients. In affected lungs, we find profuse immune cells infiltration, which likely contributes to the pro-fibrotic response via type I interferon production. The importance of type I interferons in MDA5
+
DM pathology is further emphasized by our observation in a retrospective cohort of MDA5
+
DM patients that combined calcineurin and Janus kinase inhibitor therapy show superior efficacy to calcineurin inhibitor monotherapy. In summary, this study reveals key immune-pathogenic features of MDA5
+
DM and provides a potential basis for future tailored therapies.
Anti-melanoma differentiation-associated gene 5-positive dermatomyositis is a severe autoimmune disease with largely unknown aetiology. Here authors identify the key immune cell types that contribute to the disease phenotype and implicate type I interferons signalling in the patho-mechanism.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/31
/ 13/51
/ 38/91
/ 82/1
/ CD8-Positive T-Lymphocytes - metabolism
/ Dermatomyositis - complications
/ Dermatomyositis - drug therapy
/ Etiology
/ Humanities and Social Sciences
/ Humans
/ Interferon-Induced Helicase, IFIH1
/ Kinases
/ Lung Diseases, Interstitial - complications
/ Lung Diseases, Interstitial - drug therapy
/ Melanoma
/ Science
