Gene expression profile in TNF receptor-associated periodic syndrome reveals constitutively enhanced pathways and new players in the underlying inflammation.
Clin Exp Rheumatol
; 34(6 Suppl 102): S121-S128, 2016.
Article
en En
| MEDLINE
| ID: mdl-27310036
ABSTRACT
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 IL1ß 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. TGFß 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 TGFß 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.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Monocitos
/
Regulación de la Expresión Génica
/
Mediadores de Inflamación
/
Enfermedades Autoinflamatorias Hereditarias
/
Fiebre
Tipo de estudio:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Clin Exp Rheumatol
Año:
2016
Tipo del documento:
Article
País de afiliación:
Italia