Gene expression profile in TNF receptor-associated periodic syndrome reveals constitutively enhanced pathways and new players in the underlying inflammation

Silvia Borghini, Denise Ferrera, Ignazia Prigione, Michele Fiore, Chiara Ferraris, Valentina Mirisola, Adriana Agnese Amaro, Ilaria Gueli, Luca Zammataro, Marco Gattorno, Ulrich Pfeffer, Isabella Ceccherini

Research output: Contribution to journalArticlepeer-review


OBJECTIVES: Tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is a multisystemic autoinflammatory condition associated with heterozygous TNFRSF1A mutations, presenting with a variety of clinical symptoms, many of which yet unexplained. In this work, we aimed at deepening into TRAPS pathogenic mechanisms sustained by monocytes.

METHODS: Microarray experiments were conducted to identify genes whose expression results altered in patients compared to healthy individuals, both under basal condition and following LPS stimulation.

RESULTS: An inflammatory state baseline, characterised by constitutive overexpression of IL1β and IL1R1 receptor, has been shown in TRAPS patients compared to controls, including in non-active disease phases. Following LPS stimulation, IL1RN up-regulation is stronger in controls than in patients and inflammatory pathways and microRNAs undergo differential regulation. Genes involved in post-translational modifications, protein folding and ubiquitination result constitutively up-regulated in TRAPS, while response to interferon types I and II is defective, failing to be up-regulated by LPS. TGFβ pathway is down-regulated in untreated TRAPS monocytes, while genes involved in redox regulation result constitutively over-expressed. Finally, additional molecular alterations seem to reflect organ failures sometime complicating the disease.

CONCLUSIONS: Gene expression profile in resting TRAPS monocytes has confirmed the patients' chronic inflammatory condition. In addition, pathways not yet associated with the disease have been disclosed, such as interferon types I and II response to LPS stimulation and a downregulation of the TGFβ pathway in basal condition. The role of miRNA, suggested by our results, deserves in-depth analyses in light of the possible development of targeted therapies.

Original languageEnglish
Pages (from-to)S121-S128
JournalClinical and Experimental Rheumatology
Issue number6 Suppl 102
Publication statusPublished - Oct 30 2016


  • Adolescent
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Fever
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genetic Association Studies
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Hereditary Autoinflammatory Diseases
  • Heterozygote
  • Humans
  • Inflammation Mediators
  • Interleukin 1 Receptor Antagonist Protein
  • Lipopolysaccharides
  • Male
  • Monocytes
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Polymerase Chain Reaction
  • Receptors, Tumor Necrosis Factor, Type I
  • Reproducibility of Results
  • Journal Article


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