title: Proteasome-associated autoinflammatory syndromes: advances in pathogeneses, clinical presentations, diagnosis, and management.
abstract: The disease spectrum currently known as the proteasome-associated autoinflammatory syndromes (PRAAS) was first described in 1939 in patients who presented with recurrent fevers beginning in infancy or early childhood, which were accompanied by nodular erythema, a pernio-like rash, and joint contractures. Since then, several syndromes, such as chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome, Nakajo-Nishimura syndrome (NNS), joint contractures, muscle atrophy, microcytic anemia and panniculitis-induced lipodystrophy (JMP) syndrome, and Japanese autoinflammatory syndrome with lipodystrophy (JASL), have been used to categorize patients with diseases within the same spectrum. Recently, independent studies have identified mutations in the human proteasome subunit β type 8 (PSMB8) gene, which result in a sustained inflammatory response in all syndromes. Further functional studies not only suggest a causative role of PSMB8 mutations but also imply that they represent one disease spectrum, referred to as PRAAS. In this paper, we review the clinical presentations and laboratory findings of PRAAS, as well as the most recent advances in pathogeneses, diagnosis, and treatment options for patients with diseases in this spectrum.
authors.affiliation: College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Amelia
authors.initials: A
authors.lastname: McDermott
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jacks
authors.forename: Marcus
authors.initials: M
authors.lastname: Kessler
authors.forename: Peter D
authors.initials: PD
authors.lastname: Emanuel
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
mesh_terms: D000740:Anemia / Q000235:genetics; D003286:Contracture / Q000235:genetics; D005334:Fever / Q000235:genetics; D056660:Hereditary Autoinflammatory Diseases / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D006801:Humans; D008060:Lipodystrophy / Q000235:genetics; D009133:Muscular Atrophy / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000235:genetics*; D012871:Skin Diseases / Q000235:genetics* / Q000473:pathology; D013577:Syndrome
chemical_list: C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex