Differential cytokine secretion results from p65 and c-Rel NF-κB subunit signaling in peripheral blood mononuclear cells of TNF receptor-associated periodic syndrome patients

Cell Immunol. 2011;268(2):55-9. doi: 10.1016/j.cellimm.2011.02.007. Epub 2011 Mar 1.


Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory condition caused by mutations in the TNFRSF1A gene which encodes the tumor necrosis factor (TNF) receptor, TNFR1. We investigated the effect of three high penetrance and three low penetrance TNFRSF1A mutations upon NF-κB transcription factor family subunit activity, and the resulting impact upon secretion of 25 different cytokines. Whilst certain mutations resulted in elevated NF-κB p65 subunit activity, others instead resulted in elevated c-Rel subunit activity. Interestingly, high p65 activity was associated with elevated IL-8 secretion, whereas high c-Rel activity increased IL-1β and IL-12 secretion. In conclusion, while all six TNFRSF1A mutations showed enhanced NF-κB activity, different mutations stimulated distinct NF-κB family subunit activities, and this in turn resulted in the generation of unique cytokine secretory profiles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child
  • Cytokines / immunology*
  • Female
  • Fever
  • Hereditary Autoinflammatory Diseases / blood
  • Hereditary Autoinflammatory Diseases / genetics
  • Hereditary Autoinflammatory Diseases / immunology
  • Humans
  • Immunoassay
  • Male
  • Middle Aged
  • Mutation
  • Proto-Oncogene Proteins c-rel / blood
  • Proto-Oncogene Proteins c-rel / immunology*
  • Receptors, Tumor Necrosis Factor, Type I / genetics
  • Receptors, Tumor Necrosis Factor, Type I / immunology*
  • Signal Transduction
  • Transcription Factor RelA / blood
  • Transcription Factor RelA / immunology*
  • Young Adult


  • Cytokines
  • Proto-Oncogene Proteins c-rel
  • Receptors, Tumor Necrosis Factor, Type I
  • TNFRSF1A protein, human
  • Transcription Factor RelA

Supplementary concepts

  • Periodic fever, familial, autosomal dominant