Sarcoidosis and Autoinflammation
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- Kanazawa Nobuo
- Department of Dermatology, Wakayama Medical University
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Abstract
Sporadic early-onset sarcoidosis (EOS) and familial Blau syndrome (BS) form a distinct set of autoinflammatory diseases, both of which onset in infancy and show a clinical triad of dermatitis, arthritis and uveitis histologically composed of noncaseating epithelioid cell granuloma. The responsible gene for EOS/BS is NOD2, encoding an intracellular receptor for muramyl dipeptide (MDP), the common component of bacterial cell wall peptidoglycan. The gain-of-function NOD2 mutations with MDP-independent basal NF-κB activation cause EOS/BS, while its loss-of-function mutations with impaired MDP-dependent NF-κB activation are associated with Crohn's disease and a part of sarcoidosis. As the result of analyzing genotype-phenotype relationship of Japanese EOS/BS cases, somewhat positive correlation was recognized between mutant NOD2-causing basal NF-κB activation and clinical severity, especially of ocular complications. Role of the basal NF-κB activation in monocytes has also been suggested by an inhibitory effect of thalidomide on ex vivo giant cell formation from EOS/BS patients' monocytes. Analysis of mutant NOD2-introduced human monocytic THP-1 cells, as well as the patients' samples, would provide further detailed molecular mechanisms of EOS/BS pathogenesis, in which a single point missense mutation causes a distinct pathological change forming epithelioid cell granuloma.
Journal
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- Inflammation and Regeneration
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Inflammation and Regeneration 31 (1), 66-71, 2011
The Japanese Society of Inflammation and Regeneration
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Details 詳細情報について
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- CRID
- 1390001205258231040
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- NII Article ID
- 130004943773
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- COI
- 1:CAS:528:DC%2BC3MXjs1Gmsrs%3D
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- ISSN
- 18808190
- 18809693
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- Text Lang
- en
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- Data Source
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- JaLC
- Crossref
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed