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

Tammy Martin, Zili Zhang, Paul Kurz, Carlos D. Rose, Hong Chen, Huiying Lu, Stephen Planck, Michael Davey, James (Jim) Rosenbaum

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

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
Volume60
Issue number2
DOIs
StatePublished - Feb 2009

Fingerprint

Interleukin-1
Cryopyrin-Associated Periodic Syndromes
Caspase 1
Inflammasomes
Interleukin 1 Receptor Antagonist Protein
Mutation
Interleukin-1 Receptors
Blau syndrome
Uveitis
Dermatitis
Cellular Immunity
Leucine
Arthritis
Immune System
Blood Cells
Healthy Volunteers
Inflammation
Genes
Proteins

ASJC Scopus subject areas

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

Cite this

The NOD2 defect in Blau syndrome does not result in excess interleukin-1 activity. / Martin, Tammy; Zhang, Zili; Kurz, Paul; Rose, Carlos D.; Chen, Hong; Lu, Huiying; Planck, Stephen; Davey, Michael; Rosenbaum, James (Jim).

In: Arthritis and Rheumatism, Vol. 60, No. 2, 02.2009, p. 611-618.

Research output: Contribution to journalArticle

Martin, Tammy ; Zhang, Zili ; Kurz, Paul ; Rose, Carlos D. ; Chen, Hong ; Lu, Huiying ; Planck, Stephen ; Davey, Michael ; Rosenbaum, James (Jim). / The NOD2 defect in Blau syndrome does not result in excess interleukin-1 activity. In: Arthritis and Rheumatism. 2009 ; Vol. 60, No. 2. pp. 611-618.
@article{c1d836ea12f34e6c8f43e9c21619dfa7,
title = "The NOD2 defect in Blau syndrome does not result in excess interleukin-1 activity",
abstract = "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.",
author = "Tammy Martin and Zili Zhang and Paul Kurz and Rose, {Carlos D.} and Hong Chen and Huiying Lu and Stephen Planck and Michael Davey and Rosenbaum, {James (Jim)}",
year = "2009",
month = "2",
doi = "10.1002/art.24222",
language = "English (US)",
volume = "60",
pages = "611--618",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "2",

}

TY - JOUR

T1 - The NOD2 defect in Blau syndrome does not result in excess interleukin-1 activity

AU - Martin, Tammy

AU - Zhang, Zili

AU - Kurz, Paul

AU - Rose, Carlos D.

AU - Chen, Hong

AU - Lu, Huiying

AU - Planck, Stephen

AU - Davey, Michael

AU - Rosenbaum, James (Jim)

PY - 2009/2

Y1 - 2009/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=59649127380&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=59649127380&partnerID=8YFLogxK

U2 - 10.1002/art.24222

DO - 10.1002/art.24222

M3 - Article

C2 - 19180500

AN - SCOPUS:59649127380

VL - 60

SP - 611

EP - 618

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 2

ER -