title: Mass cytometry identifies a distinct monocyte cytokine signature shared by clinically heterogeneous pediatric SLE patients.
abstract: Systemic Lupus Erythematosus (SLE) is a heterogeneous autoimmune disease with heightened disease severity in children. The incomplete understanding of the precise cellular and molecular events that drive disease activity pose a significant hurdle to the development of targeted therapeutic agents. Here, we performed single-cell phenotypic and functional characterization of pediatric SLE patients and healthy controls blood via mass cytometry. We identified a distinct CD14himonocyte cytokine signature, with increased levels of monocyte chemoattractant protein-1 (MCP1), macrophage inflammatory protein-1β (Mip1β), and interleukin-1 receptor antagonist (IL-1RA). This signature was shared by every clinically heterogeneous patient, and reproduced in healthy donors' blood upon ex-vivo exposure to plasma from clinically active patients only. This SLE-plasma induced signature was abrogated by JAK1/JAK2 selective inhibition. This study demonstrates the utility of mass cytometry to evaluate immune dysregulation in pediatric autoimmunity, by identification of a multi-parametric immune signature that can be further dissected to delineate the events that drive disease pathogenesis.
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: W E
authors.initials: WE
authors.lastname: O'Gorman
authors.affiliation: Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Kong
authors.affiliation: Department of Pediatrics, Division of Allergy, Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: I M
authors.initials: IM
authors.lastname: Balboni
authors.affiliation: Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO 80045, USA.
authors.forename: P
authors.initials: P
authors.lastname: Rudra
authors.affiliation: Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Bolen
authors.affiliation: Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO 80045, USA.
authors.forename: D
authors.initials: D
authors.lastname: Ghosh
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA; The Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Davis
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA.
authors.forename: G P
authors.initials: GP
authors.lastname: Nolan
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA; Department of Pediatrics, Division of Allergy, Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pediatrics, Division of Allergy and Immunology, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address: elena.hsieh@ucdenver.edu.
authors.forename: E W Y
authors.initials: EW
authors.lastname: Hsieh
keywords: Cytokines; JAK inhibition; MCP1; Mass cytometry; Monocytes; Pediatric systemic lupus erythematosus; Plasma circulating factors; Ruxolitinib; Type I interferons