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. 2010 Jan 18:2:3.
doi: 10.3410/M2-3.

Periodic fever syndrome and autoinflammatory diseases

Laura J Dickie  1 , Sinisa Savic, Azad Aziz, Michael Sprakes, Michael F McDermott
Affiliations

Periodic fever syndrome and autoinflammatory diseases

Laura J Dickie et al. F1000 Med Rep. .

Abstract

The concept of autoinflammatory disease as a new disease classification has resulted in a paradigm shift in our understanding of the the broad spectrum of immunological diseases. The effectiveness of interleukin-1 blockade in a variety of disorders has resulted in a marked reduction in suffering for many of these patients.

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Figures

Figure 1.
Figure 1.. Activation of the NLRP3 inflammasome leads to cleavage of pro-IL-1β, by caspase-1, into the mature IL-1β.
Activation usually occurs through stimulation with microbial peptides, such as peptidoglycan (PGN), monosodium urate (MSU), and other pathogen-associated molecular patterns (PAMP). These PAMP are recognised by the leucine-rich repeat domain (LRR) of NLRP3. Mutations in the NACHT domain of NLRP3 cause spontaneous activation of the this multimeric protein complex, which leads to over-production of IL-1β. This excessive secretion of IL-1β is mainly responsible for the clinical manifestations of the cryopyrinopathies (CAPS) and plays a role in all periodic fevers. Screening for mutations in the NACHT domain of NLRP3 is routinely carried out for diagnosis of CAPS; however mutations are only found in around 50% of cases. ASC, apoptosis-associated speck-like protein containing a CARD; bZIP, basic leucine zipper; CARD, caspase recruitment domain; CC, coiled coil; FIIND, function to find domain; MDP, muramyl dipeptide; PYD, pyrin domain; SPRY, spIA/ryanodine receptor domain.
See this image and copyright information in PMC

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