Mapping systemic lupus erythematosus heterogeneity at the single-cell level
- 2 August 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 21 (9), 1094-+
- https://doi.org/10.1038/s41590-020-0743-0
Abstract
Patients with systemic lupus erythematosus (SLE) display a complex blood transcriptome whose cellular origin is poorly resolved. Using single-cell RNA sequencing, we profiled -276,000 peripheral blood mononuclear cells from 33 children with SLE with different degrees of disease activity and 11 matched controls. Increased expression of interferon-stimulated genes (ISGs) distinguished cells from children with SLE from healthy control cells. The high ISG expression signature (ISG(hi)) derived from a small number of transcriptionally defined subpopulations within major cell types, including monocytes, CD4(+) and CD8(+) T cells, natural killer cells, conventional and plasmacytoid dendritic cells, B cells and especially plasma cells. Expansion of unique subpopulations enriched in ISGs and/or in monogenic lupus-associated genes classified patients with the highest disease activity. Profiling of similar to 82,000 single peripheral blood mononuclear cells from adults with SLE confirmed the expansion of similar subpopulations in patients with the highest disease activity. This study lays the groundwork for resolving the origin of the SLE transcriptional signatures and the disease heterogeneity towards precision medicine applications.Funding Information
- U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (CORT P50AR070594, CORT P50AR070594, CORT P50AR070594, CORT P50AR070594, CORT P50AR070594)
This publication has 59 references indexed in Scilit:
- SLE Peripheral Blood B Cell, T Cell and Myeloid Cell Transcriptomes Display Unique Profiles and Each Subset Contributes to the Interferon SignaturePLOS ONE, 2013
- Host Immune Transcriptional Profiles Reflect the Variability in Clinical Disease Manifestations in Patients with Staphylococcus aureus InfectionsPLOS ONE, 2012
- Constitutive Type I Interferon Modulates Homeostatic Balance through Tonic SignalingImmunity, 2012
- Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trialThe Lancet, 2011
- TLR recognition of self nucleic acids hampers glucocorticoid activity in lupusNature, 2010
- CD2 Distinguishes Two Subsets of Human Plasmacytoid Dendritic Cells with Distinct Phenotype and FunctionsThe Journal of Immunology, 2009
- A Modular Analysis Framework for Blood Genomics Studies: Application to Systemic Lupus ErythematosusImmunity, 2008
- Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockadeThe Journal of Experimental Medicine, 2007
- Interferon and Granulopoiesis Signatures in Systemic Lupus Erythematosus BloodThe Journal of Experimental Medicine, 2003
- Lymphopenia In Systemic Lupus ErythematosusArthritis & Rheumatism, 1978