title: Characterization of NLRP3 variants in Japanese cryopyrin-associated periodic syndrome patients.
abstract: The etiology of cryopyrin-associated periodic syndrome (CAPS) is caused by germline gene mutations in NOD-like receptor family, pryin domain containing 3 (NLRP3)/cold-induced autoinflammatory syndrome 1 (CIAS1). CAPS includes diseases with various severities. The aim of this study was to characterize patients according to the disease severity of CAPS. Five Japanese patients with four kinds of gene variations in NLRP3 were found and diagnosed as CAPS or juvenile idiopathic arthritis. Two mutations in NLRP3, Y563N and E688K, found in CAPS patients exhibit significant positive activities in the nuclear factor-κB reporter gene assay. Increased serum interleukin (IL)-18 levels were only observed in severe cases of CAPS. In mild cases of CAPS, the serum IL-18 levels were not increased, although lipopolysaccharide- or hypothermia-enhanced IL-1β and IL-18 production levels by their peripheral blood mononuclear cells were detectable. This series of case reports suggests that a combination of in vitro assays could be a useful tool for the diagnosis and characterization of the disease severity of CAPS.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan. ohnishih@gifu-u.ac.jp
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Takahide
authors.initials: T
authors.lastname: Teramoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iwata
authors.forename: Zenichiro
authors.initials: Z
authors.lastname: Kato
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kimura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kubota
authors.forename: Ryuta
authors.initials: R
authors.lastname: Nishikomori
authors.forename: Hideo
authors.initials: H
authors.lastname: Kaneko
authors.forename: Mariko
authors.initials: M
authors.lastname: Seishima
authors.forename: Naomi
authors.initials: N
authors.lastname: Kondo
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D056587:Cryopyrin-Associated Periodic Syndromes / Q000175:diagnosis / Q000235:genetics*; D016207:Cytokines / Q000097:blood; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007223:Infant; D007564:Japan; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human