J Rheum Dis.  2014 Oct;21(5):228-235. 10.4078/jrd.2014.21.5.228.

Autoinflammatory Diseases

• Lee SH

• KMID: 2222945
• DOI: http://doi.org/10.4078/jrd.2014.21.5.228

Abstract

Autoinflammatory diseases (AIDs) refer to a broad range of genetically mediated conditions characterized by recurrent attacks of systemic inflammation with typical manifestations of fever, rash, serositis, lymphadenopathy, and musculoskeletal symptoms. The discovery of genetic basis for these conditions have led to the understanding of novel intracellular receptors for infectious and noninfectious danger signals in innate immunity. Innate immunity has a key role in the development of AIDs, in contrast with autoimmune disease, which arise from problems in adaptive immunity. Advances in understanding the molecular mechanisms of intracellular inflammatory cascades have led to renewed interest in its role in the pathogenesis of more common non-genetic autoinflammatory rheumatic conditions, such as Behcet's disease, gouty arthritis, Adult onset Still's diseases, and systemic onset juvenile arthritis. The characterization of cryopyrin (inflammasome) and its significant role in the activation of proinflammatory cytokines, such as IL-1beta and TNF-alpha in the development of AIDs, has provided rational targets of anti-cytokine biologic treatment for some of these conditions.

Keyword

Inflammasome; cryopyrin; Innate immunity; Autoinflammatory rheumatic diseases

MeSH Terms

Adaptive Immunity
Adult
Arthritis, Gouty
Arthritis, Juvenile
Autoimmune Diseases
Cytokines
Exanthema
Fever
Humans
Immunity, Innate
Inflammation
Lymphatic Diseases
Serositis
Tumor Necrosis Factor-alpha
Cytokines
Tumor Necrosis Factor-alpha

Figure

• 

  Figure 1. The schematic pathway of inflammasome activation and secretion of Interleukin-1 (IL-1). PAMP: pathogen associated molecular pattern, DAMP: damage associated molecular pattern, LRR: leucin repeat region, PYD: pyrin domain, ASC: apotosis-associated speck-like protein containing CARD (A: dashed box shows detailed structure of pyrin domain).

• 

  Figure 2. Molecular targets of monogenic autoinflammatory syndromes. Mutated proteins are marked as stars. PAMP: pathogen associated molecular pattern, DAMP: damage associated molecular pattern, LRR: leucin repeat region, PYD: pyrin domain (dashed box shows detailed structure of pyrin domain).

• 

  Figure 3. Diagnostic flow sheet for evaluating autoinflammatory diseases.

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