Identification of enhanced IFN-γ signaling in polyarticular juvenile idiopathic arthritis with mass cytometry

JCI Insight. 2018 Aug 9;3(15):e121544. doi: 10.1172/jci.insight.121544.


Polyarticular juvenile idiopathic arthritis (JIA) is among the most challenging of the JIA subtypes to treat. Even with current biologic therapies, the disease remains difficult to control in a substantial subset of patients, highlighting the need for new therapies. The aim of this study was to use the high dimensionality afforded by mass cytometry with phospho-specific antibodies to delineate signaling abnormalities in immune cells from treatment-naive polyarticular JIA patients. Peripheral blood mononuclear cells were isolated from 17 treatment-naive polyarticular JIA patients, 10 of the patients after achieving clinical remission, and 19 healthy controls. Samples were stimulated for 15 minutes with IL-6 or IFN-γ and analyzed by mass cytometry. Following IFN-γ stimulation, increased STAT1 and/or STAT3 phosphorylation was observed in subsets of CD4 T cells and classical monocytes from treatment-naive patients. The enhanced IFN-γ signaling was associated with increased expression of JAK1 and SOCS1 in CD4 T cells. Furthermore, substantial heterogeneity in surface marker expression was observed among the subsets of CD4 T cells and classical monocytes with increased IFN-γ responsiveness. The identification of enhanced IFN-γ signaling in CD4 T cells and classical monocytes from treatment-naive polyarticular JIA patients provides mechanistic support for investigations into therapies that attenuate IFN-γ signaling in this disease.

Keywords: Autoimmune diseases; Immunology; Inflammation; Macrophages; T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Juvenile / blood
  • Arthritis, Juvenile / drug therapy
  • Arthritis, Juvenile / immunology*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Flow Cytometry
  • Humans
  • Infant
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism*
  • Male
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / metabolism
  • Young Adult


  • Antirheumatic Agents
  • IFNG protein, human
  • Interferon-gamma