title: Monogenic autoinflammatory diseases: disorders of amplified danger sensing and cytokine dysregulation.
abstract: The pathogenesis of monogenic autoinflammatory diseases converges on the presence of exaggerated immune responses that are triggered through activation of altered pattern recognition receptor (PRR) pathways and result in cytokine/chemokine amplification loops and the inflammatory clinical phenotype seen in autoinflammatory patients. The PRR response can be triggered by accumulation of metabolites, by mutations in sensors leading to their constitutive overactivation, or by mutations in mediator cytokine pathways that lead to amplification and/or inability to downregulate an inflammatory response in hematopoietic and/or nonhematopoietic cells. The study of the pathogenesis of sterile inflammation in patients with autoinflammatory syndromes continues to uncover novel inflammatory pathways.
authors.affiliation: Translational Autoinflammatory Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Building 10, Room 6D47-B, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Gina A Montealegre
authors.initials: GA
authors.lastname: Sanchez
authors.forename: Adriana Almeida
authors.initials: AA
authors.lastname: de Jesus
authors.forename: Raphaela
authors.initials: R
authors.lastname: Goldbach-Mansky
mesh_terms: D002352:Carrier Proteins / Q000235:genetics; D016207:Cytokines / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D056660:Hereditary Autoinflammatory Diseases / Q000235:genetics / Q000276:immunology*; D006801:Humans; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human
keywords: Autoinflammatory diseases; Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE); Cryopyrin-associated periodic syndrome (CAPS); Deficiency of the IL-1 receptor antagonist (DIRA); Inflammasome; Intracellular pattern recognition receptors (PRR); Neonatal-onset multisystem inflammatory disease (NOMID); Proteasome-associated autoinflammatory syndrome (PRAAS)