Open AccessThe NOD2 defect in Blau syndrome does not result in excess interleukin‐1 activity
Author(s) -
Martin Tammy M.,
Zhang Zili,
Kurz Paul,
Rosé Carlos D.,
Chen Hong,
Lu Huiying,
Planck Stephen R.,
Davey Michael P.,
Rosenbaum James T.
Publication year - 2009
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.24222
Subject(s) - inflammasome , nod2 , nod1 , anakinra , nalp3 , immunology , arthritis , nod , interleukin , innate immune system , immune system , caspase 1 , nod mice , medicine , inflammation , biology , cytokine , disease , endocrinology , autoimmunity , diabetes mellitus
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.