The NOD2 defect in Blau syndrome does not result in excess interleukin-1 activity

Tammy M. Martin, Zili Zhang, Paul Kurz, Carlos D. Rose, Hong Chen, Huiying Lu, Stephen R. Planck, Michael P. Davey, James T. Rosenbaum

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


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-1β (IL-1β) in cryopyrinopathies such as Muckle-Wells syndrome. Furthermore, functional studies demonstrate that caspase 1-mediated release of IL-1β also involves NOD-2. The aim of this study was to test the hypothesis that IL-1β may mediate the inflammation seen in patients with Blau syndrome. Methods. IL-1β 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-1β 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-1β-dependent autoinflammatory cryopyrinopathies, Blau syndrome is not mediated by excess IL-1β or other IL-1 activity.

Original languageEnglish (US)
Pages (from-to)611-618
Number of pages8
JournalArthritis and rheumatism
Issue number2
StatePublished - Feb 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)


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