Mass cytometry identifies a distinct monocyte cytokine signature shared by clinically heterogeneous pediatric SLE patients

W E O'Gorman; D S Kong; I M Balboni; P Rudra; C R Bolen; D Ghosh; M M Davis; G P Nolan; E W Y Hsieh

doi:10.1016/j.jaut.2017.03.010

Mass cytometry identifies a distinct monocyte cytokine signature shared by clinically heterogeneous pediatric SLE patients

J Autoimmun. 2017 Apr 4:S0896-8411(16)30412-7. doi: 10.1016/j.jaut.2017.03.010. Online ahead of print.

Authors

W E O'Gorman¹, D S Kong², I M Balboni³, P Rudra⁴, C R Bolen², D Ghosh⁴, M M Davis⁵, G P Nolan⁶, E W Y Hsieh⁷

Affiliations

¹ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
² Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
³ Department of Pediatrics, Division of Allergy, Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁴ Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO 80045, USA.
⁵ 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.
⁶ 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.
⁷ 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.

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 CD14^hi monocyte 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.

Keywords: Cytokines; JAK inhibition; MCP1; Mass cytometry; Monocytes; Pediatric systemic lupus erythematosus; Plasma circulating factors; Ruxolitinib; Type I interferons.

Abstract

Grants and funding