Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses

J Exp Med. 2019 Sep 2;216(9):1986-1998. doi: 10.1084/jem.20190344. Epub 2019 Jun 24.

Abstract

IL-6 excess is central to the pathogenesis of multiple inflammatory conditions and is targeted in clinical practice by immunotherapy that blocks the IL-6 receptor encoded by IL6R We describe two patients with homozygous mutations in IL6R who presented with recurrent infections, abnormal acute-phase responses, elevated IgE, eczema, and eosinophilia. This study identifies a novel primary immunodeficiency, clarifying the contribution of IL-6 to the phenotype of patients with mutations in IL6ST, STAT3, and ZNF341, genes encoding different components of the IL-6 signaling pathway, and alerts us to the potential toxicity of drugs targeting the IL-6R.

Publication types

  • Case Reports
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • HEK293 Cells
  • Humans
  • Immunologic Deficiency Syndromes / pathology*
  • Infant, Newborn
  • Inflammation / pathology*
  • Male
  • Receptors, Interleukin-6 / deficiency*
  • Receptors, Interleukin-6 / metabolism

Substances

  • Receptors, Interleukin-6