The NOD2 defect in Blau syndrome does not result in excess interleukin 1 activity
| Autor: | Hong Chen, Carlos D. Rose, James T. Rosenbaum, Michael P. Davey, Zili Zhang, Paul A. Kurz, Stephen R. Planck, Huiying Lu, Tammy M. Martin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Immunology Interleukin-1beta Caspase 1 Nod2 Signaling Adaptor Protein Arthritis Gene Expression Dermatitis Article Uveitis Young Adult Rheumatology NOD2 medicine Immunology and Allergy Humans Pharmacology (medical) RNA Messenger Treatment Failure Child Blau syndrome Caspase Cells Cultured Aged Innate immune system biology business.industry Interleukin Inflammasome Syndrome Middle Aged medicine.disease Interleukin 1 Receptor Antagonist Protein Antirheumatic Agents biology.protein Leukocytes Mononuclear Female business medicine.drug |
| Popis: | 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.IL-1beta release was measured in peripheral blood mononuclear cells cultured in vitro, obtained from 5 Blau syndrome individuals with a NOD2 (CARD15) mutation.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.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. |
| Databáze: | OpenAIRE |
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