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Autoinflammatory diseases are defined as illnesses caused by primary dysfunction of the innate immune system. This concept includes a broad number of diseases, initially focusing on Hereditary recurrent fevers such as the prototype FMF, Familial Mediterranean Fever. The four monogenic AIDs first described are called the 'historical' AIDs and include FMF (associated with MEFV mutations), cryopyrinopathies (associated with NLRP3 mutations), TNF receptor-associated periodic syndrome (associated with TNFRSF1A mutations) and mevalonate kinase deficiency (MKD; associated with MVK mutations). Diagnosis of monogenic AIDs is based on personal and family history and detailed analysis of symptoms associated with febrile attacks in the context of elevated peripheral inflammatory markers.
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In the last 10 years, >50 new monogenic AIDs have been discovered due to genetic advances. Molecular screening of the causative genes has dramatically improved patient quality of life, by providing early and accurate diagnosis and allowing for subsequent appropriate treatment. Some patients, however, remain hard to manage despite the advent of new genetic tests, and/or due to lack of effective treatments. The original clinical links between the hereditary recurrent fever disorders can now be confirmed by common molecular mechanisms, following the discovery that the pathogenesis involves the regulation of inflammation, particularly IL-1B, and cell death. Knowledge of the autoinflammatory disease mechanisms has already led to the elucidation of the mechanisms of action of existing drugs and may allow development of new targeted therapies.
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FMF: The Prototype disease
- Gene discovery in 1997
- Clinical criteria PubMed
List of monogenic autoinflammatory diseases
Recent reviews
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