| The NOD2 defect in Blau syndrome does not result in excess interleukin-1 activity. | |
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MedLine Citation:
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PMID: 19180500 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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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:
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Title: Arthritis and rheumatism Volume: 60 ISSN: 0004-3591 ISO Abbreviation: Arthritis Rheum. Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-02-09 Completed Date: 2009-04-01 Revised Date: 2011-03-11 |
Medline Journal Info:
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Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: United States |
Other Details:
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Languages: eng Pagination: 611-8 Citation Subset: AIM; IM |
Affiliation:
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Oregon Health & Science University, Portland, OR 79239, USA. martint@ohsu.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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K08 EY016788-05/EY/NEI NIH HHS; K08-EY-016788/EY/NEI NIH HHS; R01 EY006484-23/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:
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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:
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Arthritis Rheum. 2009 Aug;60(8):2544-5
[PMID:
19644875
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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