Evidence for the involvement of mTOR inhibition and basal autophagy in familial Mediterranean fever phenotype

Ioannis Mitroulis, Ioannis Kourtzelis, Konstantinos Kambas, Akrivi Chrysanthopoulou, Konstantinos Ritis

Research output: Contribution to journalArticlepeer-review


Familial Mediterranean fever (FMF) inflammatory attacks are often triggered by metabolic or physical stress. mTOR signaling and autophagy modulate cellular responses to metabolic danger signals. In this study, we investigated the implication of mTOR inhibition and autophagy in FMF pathophysiology. mTOR inhibition induced MEFV gene expression in polymorphonuclear cells (PMNs) from healthy individuals, whereas it had no effect on PMNs from attack-free FMF patients. A significant reduction in pyrin levels in PMNs from FMF patients after mTOR inhibition was also observed. Pyrin levels in control PMNs remained unaffected. Moreover, the basal autophagic status in PMNs from FMF patients was reduced, as indicated by the lower LC3B-II/I ratio and ATG mRNA expression levels. However, mTOR inhibition had similar effects on the induction of autophagy in the two groups. The differential pyrin expression after metabolic stress induction and the impaired basal autophagy suggest a potential role in the triggering of FMF attacks.

Original languageEnglish
Pages (from-to)135-8
Number of pages4
JournalHuman immunology
Issue number2
Publication statusPublished - Feb 2011

Bibliographical note

Copyright © 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.


  • Autophagy/drug effects
  • Cysteine Endopeptidases/immunology
  • Cytoskeletal Proteins/antagonists & inhibitors
  • Familial Mediterranean Fever/genetics
  • Gene Expression/drug effects
  • Humans
  • Mutation/immunology
  • Neutrophils/immunology
  • Phenotype
  • Pyrin
  • RNA, Messenger/biosynthesis
  • Signal Transduction/drug effects
  • Sirolimus/pharmacology
  • Stress, Physiological/drug effects
  • TOR Serine-Threonine Kinases/antagonists & inhibitors

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