You are here

  • Home
  • Archive
  • Volume 4, Issue 1
  • Single-cell gene expression patterns in lupus monocytes independently indicate disease activity, interferon and therapy

Article Text

Article menu

This article has a correction. Please see:

Download PDFPDF

Genetics
Original research article
Single-cell gene expression patterns in lupus monocytes independently indicate disease activity, interferon and therapy
  1. Zhongbo Jin1,
  2. Wei Fan1,2,
  3. Mark A Jensen1,
  4. Jessica M Dorschner1,
  5. George F Bonadurer III1,
  6. Danielle M Vsetecka1,
  7. Shreyasee Amin3,
  8. Ashima Makol3,
  9. Floranne Ernste3,
  10. Thomas Osborn3,
  11. Kevin Moder3,
  12. Vaidehi Chowdhary3 and
  13. Timothy B Niewold1
  1. 1Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA
  2. 2Department of Rheumatology, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China
  3. 3Division of Rheumatology, Mayo Clinic, Rochester, Minnesota, USA
  1. Correspondence to Dr Timothy B Niewold; niewold.timothy{at}mayo.edu

Abstract

Objectives Important findings can be masked in gene expression studies of mixed cell populations. We examined single-cell gene expression in SLE patient monocytes in the context of clinical and immunological features.

Methods Monocytes were purified from patients with SLE and controls, and individually isolated for single-cell gene expression measurement. A panel of monocyte-related transcripts were measured in individual classical (CL) and non-classical (NCL) monocytes.

Results Analyses of both CL and NCL monocytes demonstrated that many genes had a lower expression rate in SLE monocytes than in controls. Unsupervised hierarchical clustering of the CL and NCL data sets demonstrated independent clusters of cells from the patients with SLE that were related to disease activity, type I interferon (IFN) and medication use. Thus, each of these factors exerted a different impact on monocyte gene expression that could be identified separately, and a number of genes correlated uniquely with disease activity. We found within-cell correlations between genes directly induced by type I IFN-induced and other non–IFN-induced genes, suggesting the downstream biological effects of type I IFN in individual human SLE monocytes which differed between CLs and NCLs.

Conclusions In summary, single-cell gene expression in monocytes was associated with a wide range of clinical and biological features in SLE, providing much greater detail and insight into the cellular biology underlying the disease than previous mixed-cell population studies.

  • Systemic Lupus Erythematosus
  • Cytokines
  • Autoimmunity

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/lupus-2016-000202

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Footnotes

    • Contributors ZJ, WF, MAJ, JMD and GFB performed experiments, analysed data andcontributed to writing the manuscript. DMV, SA, AM, FE, TO, KM and VC recruited patients and collected patientdata, analysed data and contributed to the manuscript. TBN designed and supervised the study,revised the paper and performed data analysis and interpretation.

    • Funding WF: National Nature Science Foundation of China Grant No. 81402934; MAJ: Lupus Research Institute, Mayo Clinic Foundation; TBN: NIH grants (AR060861, AR057781, AR065964, AI071651), Rheumatology Research Foundation, the Mayo Clinic Foundation, the Lupus Research Institute, and the Lupus Foundation of Minnesota.

    • Competing interests None declared.

    • Ethics approval Mayo Clinic Institutional Review Board.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Author note Zhongbo Jin and Wei Fan are co-first authors.

    • Correction notice The content of this article has been corrected since it first published Online First. Figure 3 has been replaced and the co-first authorship of the paper has been indicated.