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.
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).
Published by Elsevier Inc.