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 CD14hi 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.

miR-126 in Peripheral Blood Mononuclear Cells Negatively Correlates with Risk and Severity and is Associated with Inflammatory Cytokines as well as Intercellular Adhesion Molecule-1 in Patients with Coronary Artery Disease

“…miR-126 PBMC expression is notably decreased in systemic lupus erythematosus patients and downregulates the interferon production [35]. Furthermore, inflammatory cytokines are produced by lymphocytes and monocytes, suggesting that PBMC miR-126 correlated with the inflammatory cytokines might result from miR-126 being involved in the production of inflammatory cytokines by PBMCs [31,32,33,36,37]. …”

Single-Cell Mass Cytometry on Peripheral Blood Identifies Immune Cell Subsets Associated with Primary Biliary Cholangitis

“…This technology utilizes heavy-metal ion tags instead of fluorophores to detect target-bound monoclonal antibodies, allowing for simultaneous quantification of 40 or more cell markers 11 . This increased dimensionality facilitates a more comprehensive survey of immune composition and has recently been employed in the examination of peripheral blood in various pathologies, including autoimmune diseases and cancers [12][13][14] .…”

“…FlowSOM metacluster analysis.Metaclusters 12,13,14,15,17,19, and 20 were excluded from this table due to their lack of CD45 expression or their having a mean abundance of <0.1%. ‡ Cirrhosis information was unavailable for one patient.…”

Advances in high-dimensional mass cytometry cell and tissue analyses for translational biomarker discovery

“…Ultimately these data aid in the development of disease diagnostic and prognostic tools, and more importantly determine patient stratification strategies which enable personalized medicine approaches. The focus of this review is to highlight the value of the translational data generated using novel technologies, such as mass cytometry (MC) and imaging MC, which has brought single cell immunophenotyping and imaging of the tumor microenvironment and other tissues to a new forefront, and to review emerging data tools which enable comprehensive data analysis and interpretation, often identifying previously unrecognized connections between cellular phenotypes and functions in healthy and diseased states [9][10][11][12].Although still in early development, MC based single cell immunophenotyping and analysis are steadily gaining recognition and becoming a mainstay in not only immune-mediated disease research, but in interrogating basic biology of other therapeutic targets [13][14][15][16]. MC or cytometry by time of flight (CyTOF) merges concepts of both flow cytometry and mass spectrometry [17,18].…”

“…Ultimately these data aid in the development of disease diagnostic and prognostic tools, and more importantly determine patient stratification strategies which enable personalized medicine approaches. The focus of this review is to highlight the value of the translational data generated using novel technologies, such as mass cytometry (MC) and imaging MC, which has brought single cell immunophenotyping and imaging of the tumor microenvironment and other tissues to a new forefront, and to review emerging data tools which enable comprehensive data analysis and interpretation, often identifying previously unrecognized connections between cellular phenotypes and functions in healthy and diseased states [9][10][11][12].…”