Document Detail


The NOD2 defect in Blau syndrome does not result in excess interleukin-1 activity.
MedLine Citation:
PMID:  19180500     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Blau syndrome is a rare, autosomal-dominant, autoinflammatory disorder characterized by granulomatous arthritis, uveitis, and dermatitis. Genetics studies have shown that the disease is caused by single nonsynonymous substitutions in NOD-2, a member of the NOD-like receptor or NACHT-leucine-rich repeat (NLR) family of intracellular proteins. Several NLRs function in the innate immune system as sensors of pathogen components and participate in immune-mediated cellular responses via the caspase 1 inflammasome. Mutations in a gene related to NOD-2, NLRP3, are responsible for excess caspase 1-dependent interleukin-1beta (IL-1beta) in cryopyrinopathies such as Muckle-Wells syndrome. Furthermore, functional studies demonstrate that caspase 1-mediated release of IL-1beta also involves NOD-2. The aim of this study was to test the hypothesis that IL-1beta may mediate the inflammation seen in patients with Blau syndrome.
METHODS: IL-1beta release was measured in peripheral blood mononuclear cells cultured in vitro, obtained from 5 Blau syndrome individuals with a NOD2 (CARD15) mutation.
RESULTS: We observed no evidence for increased IL-1beta production in cells obtained from subjects with Blau syndrome compared with healthy control subjects. Furthermore, we presented 2 cases of Blau syndrome in which recombinant human IL-1 receptor antagonist (anakinra) was ineffective treatment.
CONCLUSION: Taken together, these data suggest that in contrast to related IL-1beta-dependent autoinflammatory cryopyrinopathies, Blau syndrome is not mediated by excess IL-1beta or other IL-1 activity.
Authors:
Tammy M Martin; Zili Zhang; Paul Kurz; Carlos D Rosé; Hong Chen; Huiying Lu; Stephen R Planck; Michael P Davey; James T Rosenbaum
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  60     ISSN:  0004-3591     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-09     Completed Date:  2009-04-01     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  611-8     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Antirheumatic Agents / therapeutic use
Arthritis / drug therapy,  genetics*,  metabolism
Cells, Cultured
Child
Dermatitis / drug therapy,  genetics*,  metabolism
Female
Gene Expression
Humans
Interleukin 1 Receptor Antagonist Protein / therapeutic use
Interleukin-1beta / genetics*,  metabolism
Leukocytes, Mononuclear / drug effects,  metabolism
Male
Middle Aged
Nod2 Signaling Adaptor Protein / genetics*,  metabolism
RNA, Messenger / metabolism
Syndrome
Treatment Failure
Uveitis / drug therapy,  genetics*,  metabolism
Young Adult
Grant Support
ID/Acronym/Agency:
K08 EY016788-05/EY/NEI NIH HHS; K08-EY-016788/EY/NEI NIH HHS; R01 EY006484/EY/NEI NIH HHS; R01 EY006484-23/EY/NEI NIH HHS; R01 EY013139/EY/NEI NIH HHS; R01 EY013139-07/EY/NEI NIH HHS; R01 EY013139-08/EY/NEI NIH HHS; R01-EY-006484/EY/NEI NIH HHS; R01-EY-013139/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Antirheumatic Agents; 0/Interleukin 1 Receptor Antagonist Protein; 0/Interleukin-1beta; 0/NOD2 protein, human; 0/Nod2 Signaling Adaptor Protein; 0/RNA, Messenger
Comments/Corrections
Comment In:
Arthritis Rheum. 2009 Aug;60(8):2544-5   [PMID:  19644875 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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