Source:http://linkedlifedata.com/resource/pubmed/id/18063752
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
2008-2-11
|
| pubmed:abstractText |
Cryopyrin-associated periodic syndrome (CAPS) is a spectrum of systemic autoinflammatory disorders in which the majority of patients have mutations in the cold-induced autoinflammatory syndrome (CIAS)1 gene. Despite having indistinguishable clinical features, some patients lack CIAS1 mutations by conventional nucleotide sequencing. We recently reported a CAPS patient with mosaicism of mutant CIAS1, and raised the possibility that CIAS1 mutations were overlooked in "mutation-negative" patients, due to a low frequency of mosaicism. To determine whether there were latent mutant cells in "mutation-negative" patients, we sought to identify mutation-associated biologic phenotypes of patients' monocytes. We found that lipopolysaccharide selectively induced necrosis-like cell death in monocytes bearing CIAS1 mutations. Monocyte death correlated with CIAS1 up-regulation, was dependent on cathepsin B, and was independent of caspase-1. Cell death was intrinsic to CIAS1-mutated monocytes, was not mediated by the inflammatory milieu, and was independent of disease severity or anti-IL-1 therapy. By collecting dying monocytes after lipopolysaccharide treatment, we succeeded in enriching CIAS1-mutant monocytes and identifying low-level CIAS1-mosaicism in 3 of 4 "mutation-negative" CAPS patients. Our findings reveal a novel effect of CIAS1 mutations in promoting necrosis-like cell death, and demonstrate that CIAS1 mosaicism plays an important role in mutation-negative CAPS patients.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
0006-4971
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| pubmed:author |
pubmed-author:AdachiSouichiS,
pubmed-author:FujisawaAkihiroA,
pubmed-author:HeikeToshioT,
pubmed-author:IeharaTomokoT,
pubmed-author:ImagawaTomoyukiT,
pubmed-author:KagamiShinjiS,
pubmed-author:KambeNaotomoN,
pubmed-author:KawakamiKiyoshiK,
pubmed-author:KawashimaHisashiH,
pubmed-author:MatsubayashiTadashiT,
pubmed-author:MiyachiYoshikiY,
pubmed-author:NakahataTatsutoshiT,
pubmed-author:NishikomoriRyutaR,
pubmed-author:OkafujiIkuoI,
pubmed-author:SaitoMegumuM,
pubmed-author:TakadaHidetoshiH,
pubmed-author:TakeichiKyokoK,
pubmed-author:TanakaHiroshiH,
pubmed-author:TanizakiHideakiH,
pubmed-author:YoshiokaTakakazuT
|
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
111
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2132-41
|
| pubmed:dateRevised |
2011-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:18063752-Amyloidosis,
pubmed-meshheading:18063752-Carrier Proteins,
pubmed-meshheading:18063752-Cell Death,
pubmed-meshheading:18063752-Chromosome Aberrations,
pubmed-meshheading:18063752-Deafness,
pubmed-meshheading:18063752-Female,
pubmed-meshheading:18063752-Humans,
pubmed-meshheading:18063752-Inflammation,
pubmed-meshheading:18063752-Intellectual Disability,
pubmed-meshheading:18063752-Male,
pubmed-meshheading:18063752-Meningitis,
pubmed-meshheading:18063752-Monocytes,
pubmed-meshheading:18063752-Mosaicism,
pubmed-meshheading:18063752-Mutation,
pubmed-meshheading:18063752-Skin Diseases,
pubmed-meshheading:18063752-Syndrome
|
| pubmed:year |
2008
|
| pubmed:articleTitle |
Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients.
|
| pubmed:affiliation |
Departments of Pediatrics, Kyoto University Graduate School of Medicine, Shogoin, Sakyo-ku, Kyoto, Japan.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|