Mapping systemic lupus erythematosus heterogeneity at the single-cell level

Djamel Nehar-Belaid, Seunghee Hong, Radu Marches, Guo Chen, Mohan Bolisetty, Jeanine Baisch, Lynnette Walters, Marilynn Punaro, Robert J. Rossi, Cheng Han Chung, Richie P. Huynh, Prashant Singh, William F. Flynn, Joy Ann Tabanor-Gayle, Navya Kuchipudi, Asuncion Mejias, Magalie A. Collet, Anna Lisa Lucido, Karolina Palucka, Paul RobsonSanthanam Lakshminarayanan, Octavio Ramilo, Tracey Wright, Virginia Pascual, Jacques F. Banchereau

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

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 (ISGhi) 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 ~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.

Original languageEnglish
Pages (from-to)1094-1106
Number of pages13
JournalNature Immunology
Volume21
Issue number9
DOIs
Publication statusPublished - 2020 Sep 1

Bibliographical note

Funding Information:
We are grateful to the patients with SLE, their families, the healthy individuals who participated in our study and the members of the Pediatric Rheumatology Clinics at Texas Scottish Rite Hospital for Children and the Children’s Medical Center in Dallas, TX and M. Sansone, T. Jackson and F. Jawed for help with recruiting adults with SLE. We gratefully acknowledge the contribution of Flow Cytometry, Single Cell Biology and Genome Technologies Scientific Services at The Jackson Laboratory, which are partially supported by NCI P30CA034196, and thank them for expert assistance with the work described in this publication. In addition, we thank JAX Research IT (particularly Sandeep Namburi) for the support with maintaining the R Shiny application. This work was supported by grants NIAMS CORT P50AR070594 Center for Lupus Research (to V.P. and J.F.B.), NIAID NIH U19 AI082715 (to V.P.) and U01 AI131386 (to O.R. and J.F.B.) and start-up funds from the Jackson Laboratory and the Drukier Institute for Children’s Health at Weill Cornell Medicine.

Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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