An autoinflammatory disease due to homozygous deletion of the IL1RN locus.
Sreelatha T. Reddy,Shuang Jia,Rhonda Geoffrey,Rachel Lorier,Mariko Suchi,Ulrich Broeckel,Martin J. Hessner,James W. Verbsky +7 more
Reads0
Chats0
TLDR
A patient with an autoinflammatory disease in which the main clinical features are pustular rash, marked osteopenia, lytic bone lesions, respiratory insufficiency, and thrombosis is described, which contains a 175-kb homozygous deletion at chromosome 2q13, which encompasses several interleukin-1 family members.Abstract:
We describe a patient with an autoinflammatory disease in which the main clinical features are pustular rash, marked osteopenia, lytic bone lesions, respiratory insufficiency, and thrombosis. Genetic studies revealed a 175-kb homozygous deletion at chromosome 2q13, which encompasses several interleukin-1 family members, including the gene encoding the interleukin-1–receptor antagonist (IL1RN). Mononuclear cells, obtained from the patient and cultured, produced large amounts of inflammatory cytokines, with increasing amounts secreted after stimulation with lipopolysaccharide. A similar increase was not observed in peripheral-blood mononuclear cells from a patient with neonatal-onset multisystem inflammatory disorder (NOMID). Treatment with anakinra completely resolved the symptoms and lesions.read more
Citations
More filters
Journal ArticleDOI
Interleukin-1 in the pathogenesis and treatment of inflammatory diseases
TL;DR: This review summarizes acute and chronic inflammatory diseases that are treated by reducing IL-1β activity and proposes that disease severity is affected by the anti-inflammatory members of the IL- 1 family of ligands and receptors.
Journal ArticleDOI
The Interleukin-1 Family: Back to the Future
TL;DR: The key properties of IL-1 family members are reviewed, with emphasis on pathways of negative regulation and orchestration of innate and adaptive immunity.
Journal ArticleDOI
Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases
TL;DR: Monotherapy blocking IL-1 activity in autoinflammatory syndromes results in a rapid and sustained reduction in disease severity, including reversal of inflammation-mediated loss of sight, hearing and organ function.
Journal ArticleDOI
The IL-1 family: regulators of immunity
John E. Sims,Dirk E. Smith +1 more
TL;DR: This Review provides an overview of both the long-established and more recently characterized members of the IL-1 family and their effects on immune cells, their involvement in human disease and disease models is discussed.
Journal ArticleDOI
Anti-inflammatory Agents: Present and Future
TL;DR: The new era of anti-inflammatory agents includes "biologicals" such as anticytokine therapies and small molecules that block the activity of kinases and small RNAs.
References
More filters
Journal ArticleDOI
Genesis: cluster analysis of microarray data
TL;DR: Genesis integrates various tools for microarray data analysis such as filters, normalization and visualization tools, distance measures as well as common clustering algorithms including hierarchical clustering, self-organizing maps, k-means, principal component analysis, and support vector machines.
Journal ArticleDOI
NALP3 Forms an IL-1β-Processing Inflammasome with Increased Activity in Muckle-Wells Autoinflammatory Disorder
Laetitia Agostini,Fabio Martinon,Kimberly Burns,Michael F. McDermott,Philip N. Hawkins,Jürg Tschopp +5 more
TL;DR: It is reported that NALP2 and NalP3 associate with ASC, the CARD-containing protein Cardinal, and caspase-1 (but not casp enzyme-5), thereby forming an inflammasome with high proIL-1beta-processing activity.
Journal ArticleDOI
Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle–Wells syndrome
Hal M. Hoffman,James L. Mueller,David H. Broide,Alan A. Wanderer,Richard D. Kolodner,Richard D. Kolodner +5 more
TL;DR: A gene, called CIAS1, is expressed in peripheral blood leukocytes and encodes a protein with a pyrin domain, a nucleotide-binding site (NBS, NACHT subfamily) domain and a leucine-rich repeat (LRR) motif region, suggesting a role in the regulation of inflammation and apoptosis.
Journal ArticleDOI
Human T Regulatory Cells Can Use the Perforin Pathway to Cause Autologous Target Cell Death
William Grossman,James W. Verbsky,Winfried Barchet,Marco Colonna,John P. Atkinson,Timothy J. Ley +5 more
TL;DR: It is demonstrated that activated human CD4(+)CD25(+) natural Treg cells express granzyme A but very little granzyme B, which suggests that the perforin/granzyme pathway is one of the mechanisms that T Reg cells can use to control immune responses.
Journal ArticleDOI
An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist
Ivona Aksentijevich,Seth L. Masters,Polly J. Ferguson,Paul Dancey,Joost Frenkel,Annet van Royen-Kerkhoff,R. M. Laxer,Ulf Tedgård,Edward W. Cowen,Tuyet-Hang Pham,Matthew G. Booty,Jacob D. Estes,Netanya G. Sandler,Nicole Plass,Deborah L. Stone,Maria L. Turner,Suvimol Hill,John A. Butman,Rayfel Schneider,Paul Babyn,Hatem El-Shanti,Elena Pope,Karyl S. Barron,Xinyu Bing,Arian Laurence,Chyi-Chia Richard Lee,Dawn Chapelle,Gillian I. Clarke,Kamal Ohson,Marc Nicholson,Massimo Gadina,Barbara Yang,Benjamin D. Korman,Peter K. Gregersen,P. Martin van Hagen,A. Elisabeth Hak,Marjan Huizing,Proton Rahman,Daniel C. Douek,Elaine F. Remmers,Daniel L. Kastner,Raphaela Goldbach-Mansky +41 more
TL;DR: The term deficiency of the interleukin-1-receptor antagonist, or DIRA, is proposed to denote this autosomal recessive autoinflammatory disease caused by mutations affecting IL1RN, resulting in life-threatening systemic inflammation with skin and bone involvement.
Related Papers (5)
An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist
Ivona Aksentijevich,Seth L. Masters,Polly J. Ferguson,Paul Dancey,Joost Frenkel,Annet van Royen-Kerkhoff,R. M. Laxer,Ulf Tedgård,Edward W. Cowen,Tuyet-Hang Pham,Matthew G. Booty,Jacob D. Estes,Netanya G. Sandler,Nicole Plass,Deborah L. Stone,Maria L. Turner,Suvimol Hill,John A. Butman,Rayfel Schneider,Paul Babyn,Hatem El-Shanti,Elena Pope,Karyl S. Barron,Xinyu Bing,Arian Laurence,Chyi-Chia Richard Lee,Dawn Chapelle,Gillian I. Clarke,Kamal Ohson,Marc Nicholson,Massimo Gadina,Barbara Yang,Benjamin D. Korman,Peter K. Gregersen,P. Martin van Hagen,A. Elisabeth Hak,Marjan Huizing,Proton Rahman,Daniel C. Douek,Elaine F. Remmers,Daniel L. Kastner,Raphaela Goldbach-Mansky +41 more
Germline mutations in the extracellular domains of the 55 kda tnf receptor, tnfr1, define a family of dominantly inherited autoinflammatory syndromes
Michael F. McDermott,Ivona Aksentijevich,Jérôme Galon,Elizabeth M. McDermott,B. William Ogunkolade,Michael Centola,Elizabeth Mansfield,Massimo Gadina,Leena Karenko,Tom Pettersson,John McCarthy,David M. Frucht,Martin Aringer,Yelizaveta Torosyan,Anna-Maija Teppo,Meredith Wilson,H.Mehmet Karaarslan,Ying Wan,Ian Todd,Geryl Wood,Ryan Schlimgen,Thisum R. Kumarajeewa,Sheldon M. Cooper,John P. Vella,Christopher I. Amos,John C. Mulley,Kathleen A. Quane,Michael G. Molloy,Annamari Ranki,Richard J. Powell,Graham A. Hitman,John J. O'Shea,Daniel L. Kastner +32 more
Neonatal-Onset Multisystem Inflammatory Disease Responsive to Interleukin-1β Inhibition
Raphaela Goldbach-Mansky,Natalie J Dailey,Scott W. Canna,Ana Gelabert,Janet Jones,Benjamin I. Rubin,H. Jeffrey Kim,Carmen C. Brewer,Christopher K. Zalewski,Edythe Wiggs,Suvimol Hill,Maria L. Turner,Barbara I. Karp,Ivona Aksentijevich,Frank Pucino,Scott R. Penzak,Margje H. Haverkamp,Leonard D. Stein,Barbara S. Adams,Terry L. Moore,Robert C. Fuhlbrigge,Bracha Shaham,James N. Jarvis,Kathleen M. O'Neil,Richard K. Vehe,Laurie O Beitz,Gregory C. Gardner,William P Hannan,Robert W. Warren,William Horn,Joe L Cole,Scott M. Paul,Philip N. Hawkins,T. Pham,Christopher Snyder,Robert Wesley,Steven C. Hoffmann,Steven M. Holland,John A. Butman,Daniel L. Kastner +39 more