Down Syndrome, Interferonopathy and Interferon receptor genes

Reference: Kong, X., Worley, L., Rinchai, D. et al. Three Copies of Four Interferon Receptor Genes Underlie a Mild Type I Interferonopathy in Down Syndrome. J Clin Immunol (2020)

Journal: Journal of Clinical Immunology


  1. 45 Down syndrome (DS) patients were evaluated by flow-cytometry, transcriptomics, ELISA and EMSA to study the clinical and cellular phenotype with emphasis on development of Th17 cells and its role in infections and autoimmunity 
  2. Surface expression of IFN-αR1, IFN-αR2, IFN-γR2 and IL-10RB are abnormally high on EBV-B cell in DS compared to healthy controls and they also showed increased response to IFN-α and IFN-γ, but not to IL-6 or IL-21
  3. DS patients also show increased expression of IFN-αR1, IFN-αR2, and IFN-γR2 with high STAT1 and pSTAT1 levels on monocytes
  4. They also have unregulated Interferon-stimulated gene in monocytes and increased levels of type I IFN proteins in plasma
  5. DS patients have low naive CD4+ T cells,  high Terminal effector T cells and normal Th17 cell count

Bottom line: Enhanced IFN response may be targeted by JAK-STAT inhibitors to control chronic mucocutaneous candidiasis and autoimmunity in DS patients. Down’s syndrome may be considered a part of type I interferonopathies