Familial Mediterranean fever and related periodic fever syndromes/autoinflammatory diseases.

Abstract

PURPOSE OF REVIEW:

The spectrum of periodic fever syndromes (PFS)/autoinflammation diseases is continuously expanding. This review provides an overview of the primary research and an update on the main clinical developments in these disorders published in the past 12-18 months.

RECENT FINDINGS:

IL-1β is pivotal to the pathogenesis of most of the PFS. In familial Mediterranean fever (FMF) MEFV mutations lead to gain of pyrin function, resulting in inappropriate IL-1β release that is dependent on ASC but not the NLRP3 inflammasome. Anti-IL-1 therapy is effective in tumour necrosis factor receptor-associated periodic syndrome (TRAPS), whilst both spontaneous and pathogen-associated molecular patterns (PAMPs) induced IL-1β release have been demonstrated in NLRP12-associated periodic syndrome (NAPS12). Somatic NLRP3/CIAS1 mosaicism is a significant cause of cryopyrin-associated periodic syndromes (CAPS). Close connections have also been established between metabolic and inflammatory pathways. In TRAPS increased reactive oxygen species (ROS) of mitochondrial origin leads to production of pro-inflammatory cytokines, whilst NLRP3 inflammasome activation in type 2 diabetes (T2D) is induced by oligomers of islet amyloid polypeptides (IAPP).

SUMMARY:

Caspase 1 activation and IL-1β release is central to the pathogenesis of many autoinflammatory syndromes. This is supported by the effectiveness of anti-IL-1 biologics in treatment of these disorders.

• Authors: Sinisa Savic, Laura J Dickie, Michele Battellino, Michael F McDermott
• Journal: Current opinion in rheumatology (Curr Opin Rheumatol) Vol. 24 Issue 1 Pg. 103-12 (Jan 2012) ISSN: 1531-6963 [Electronic] United States
• PMID: 22089100 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Interleukin-1beta
• Caspase 1

Topics

• Caspase 1 (metabolism)
• Familial Mediterranean Fever (drug therapy, etiology, metabolism)
• Humans
• Interleukin-1beta (metabolism)
• Mevalonate Kinase Deficiency (drug therapy, etiology, metabolism)