title: Anakinra improves sensory deafness in a Japanese patient with Muckle-Wells syndrome, possibly by inhibiting the cryopyrin inflammasome.
abstract: Muckle-Wells syndrome (MWS) is a dominantly inherited autoinflammatory syndrome. Patients with MWS have a mutation in CIAS1, the gene encoding cryopyrin, a component of the inflammasome that regulates the processing of interleukin-1beta (IL-1beta). In this report we describe an 8-year-old Japanese girl with MWS who had symptoms of periodic fever, urticarial rash, conjunctivitis, arthropathy, and sensory deafness. Laboratory analysis of the patient's serum showed abnormally high concentrations of C-reactive protein, serum amyloid A, and IL-1beta, and she had a heterozygous mutation in the CIAS1 gene, with C-to-T transversion at nucleotide position 778, encoding an arginine-to-tryptophan mutation at position 260 (R260W). Mononuclear cells (MNCs) isolated from the patient secreted large amounts of IL-1beta, without stimulation, and were highly sensitive to muramyldipeptide and lipopolysaccharide. After treatment with anakinra, laboratory results normalized, and clinical symptoms, including sensory deafness, disappeared, while MNCs appeared to remain activated. Thus, our case suggests that anakinra possibly affects the cryopyrin inflammasome and markedly improves the clinical and laboratory manifestations of MWS.
authors.affiliation: Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Junya
authors.initials: J
authors.lastname: Masumoto
authors.forename: Kazunaga
authors.initials: K
authors.lastname: Agematsu
authors.forename: Nobukuni
authors.initials: N
authors.lastname: Sawai
authors.forename: Shinji
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Tomonari
authors.initials: T
authors.lastname: Shigemura
authors.forename: Kozo
authors.initials: K
authors.lastname: Yasui
authors.forename: Kenichi
authors.initials: K
authors.lastname: Koike
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000150:complications* / Q000235:genetics; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D002648:Child; D003231:Conjunctivitis / Q000150:complications / Q000235:genetics; D003638:Deafness / Q000188:drug therapy* / Q000209:etiology* / Q000235:genetics; D005076:Exanthema / Q000150:complications / Q000235:genetics; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000097:blood; D009154:Mutation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D013577:Syndrome
chemical_list: D018501:Antirheumatic Agents; D002352:Carrier Proteins; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human