Monogenic autoinflammatory diseases: New insights into clinical aspects and pathogenesis

Cailin Sibley, Raphaela Goldbach-Mansky

Research output: Contribution to journalReview article

52 Citations (Scopus)

Abstract

Purpose Of Review: The genetic and clinical characterizations of monogenic autoinflammatory syndromes have led to ground breaking insights into the regulation of inflammatory responses to endogenous and exogenous inducers or triggers of inflammation and continue to uncover key inflammatory pathways of the innate immune system. This article summarizes recent progress in the clinical aspects and understanding of the pathogenesis of this growing spectrum of diseases. Recent Findings: The understanding of the spectrum of organ manifestations in autoinflammation was expanded by the discovery of two novel monogenic diseases both caused by the absence of an anti-inflammatory signal and added evidence that increased IL-1 signaling can cause aseptic osteolytic bone lesions and that the absence of IL-10 signaling causes inflammatory enterocolitis in neonates. New knock in animal models for TNF-receptor- associated periodic syndrome, and familial Mediterranean fever and cryopyrin-associated periodic syndromes allow insights into the complexity of the dysregulated immune pathways. Exploring 'triggers' of the NLRP3 inflammasome spurred studies of tissue inflammation in diseases including gout and those that previously have not been considered inflammatory in nature such as diabetes, fibrosing lung disease and possibly coronary artery disease. Summary: The genetic characterization of a growing number of monogenic autoinflammatory diseases has provided important insights into the phenotypic expression of single gene disorders and the complexity of the dysregulated inflammatory pathways leading to clinical disease. Knowledge obtained from these disorders is pertinent to a number of common disorders and provides new targets for drug development.

Original languageEnglish (US)
Pages (from-to)567-578
Number of pages12
JournalCurrent Opinion in Rheumatology
Volume22
Issue number5
DOIs
StatePublished - 2010
Externally publishedYes

Fingerprint

Cryopyrin-Associated Periodic Syndromes
Inflammasomes
Inflammation
Familial Mediterranean Fever
Enterocolitis
Gout
Interleukin-1
Interleukin-10
Lung Diseases
Coronary Artery Disease
Immune System
Anti-Inflammatory Agents
Animal Models
Gene Expression
Bone and Bones
Pharmaceutical Preparations
Autosomal Dominant Familial Periodic Fever

Keywords

  • autoinflammatory diseases
  • cryopyrin-associated periodic syndromes
  • deficiency of the IL-1 receptor antagonist
  • familial Mediterranean fever
  • hyperimmunoglobulinemia D with periodic fevers syndrome
  • IL-1
  • inflammasome
  • TNF-receptor-associated periodic syndrome

ASJC Scopus subject areas

  • Rheumatology

Cite this

Monogenic autoinflammatory diseases : New insights into clinical aspects and pathogenesis. / Sibley, Cailin; Goldbach-Mansky, Raphaela.

In: Current Opinion in Rheumatology, Vol. 22, No. 5, 2010, p. 567-578.

Research output: Contribution to journalReview article

Sibley, Cailin ; Goldbach-Mansky, Raphaela. / Monogenic autoinflammatory diseases : New insights into clinical aspects and pathogenesis. In: Current Opinion in Rheumatology. 2010 ; Vol. 22, No. 5. pp. 567-578.
@article{f0b1396764a845f4960da78277f0a014,
title = "Monogenic autoinflammatory diseases: New insights into clinical aspects and pathogenesis",
abstract = "Purpose Of Review: The genetic and clinical characterizations of monogenic autoinflammatory syndromes have led to ground breaking insights into the regulation of inflammatory responses to endogenous and exogenous inducers or triggers of inflammation and continue to uncover key inflammatory pathways of the innate immune system. This article summarizes recent progress in the clinical aspects and understanding of the pathogenesis of this growing spectrum of diseases. Recent Findings: The understanding of the spectrum of organ manifestations in autoinflammation was expanded by the discovery of two novel monogenic diseases both caused by the absence of an anti-inflammatory signal and added evidence that increased IL-1 signaling can cause aseptic osteolytic bone lesions and that the absence of IL-10 signaling causes inflammatory enterocolitis in neonates. New knock in animal models for TNF-receptor- associated periodic syndrome, and familial Mediterranean fever and cryopyrin-associated periodic syndromes allow insights into the complexity of the dysregulated immune pathways. Exploring 'triggers' of the NLRP3 inflammasome spurred studies of tissue inflammation in diseases including gout and those that previously have not been considered inflammatory in nature such as diabetes, fibrosing lung disease and possibly coronary artery disease. Summary: The genetic characterization of a growing number of monogenic autoinflammatory diseases has provided important insights into the phenotypic expression of single gene disorders and the complexity of the dysregulated inflammatory pathways leading to clinical disease. Knowledge obtained from these disorders is pertinent to a number of common disorders and provides new targets for drug development.",
keywords = "autoinflammatory diseases, cryopyrin-associated periodic syndromes, deficiency of the IL-1 receptor antagonist, familial Mediterranean fever, hyperimmunoglobulinemia D with periodic fevers syndrome, IL-1, inflammasome, TNF-receptor-associated periodic syndrome",
author = "Cailin Sibley and Raphaela Goldbach-Mansky",
year = "2010",
doi = "10.1097/BOR.0b013e32833ceff4",
language = "English (US)",
volume = "22",
pages = "567--578",
journal = "Current Opinion in Rheumatology",
issn = "1040-8711",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Monogenic autoinflammatory diseases

T2 - New insights into clinical aspects and pathogenesis

AU - Sibley, Cailin

AU - Goldbach-Mansky, Raphaela

PY - 2010

Y1 - 2010

N2 - Purpose Of Review: The genetic and clinical characterizations of monogenic autoinflammatory syndromes have led to ground breaking insights into the regulation of inflammatory responses to endogenous and exogenous inducers or triggers of inflammation and continue to uncover key inflammatory pathways of the innate immune system. This article summarizes recent progress in the clinical aspects and understanding of the pathogenesis of this growing spectrum of diseases. Recent Findings: The understanding of the spectrum of organ manifestations in autoinflammation was expanded by the discovery of two novel monogenic diseases both caused by the absence of an anti-inflammatory signal and added evidence that increased IL-1 signaling can cause aseptic osteolytic bone lesions and that the absence of IL-10 signaling causes inflammatory enterocolitis in neonates. New knock in animal models for TNF-receptor- associated periodic syndrome, and familial Mediterranean fever and cryopyrin-associated periodic syndromes allow insights into the complexity of the dysregulated immune pathways. Exploring 'triggers' of the NLRP3 inflammasome spurred studies of tissue inflammation in diseases including gout and those that previously have not been considered inflammatory in nature such as diabetes, fibrosing lung disease and possibly coronary artery disease. Summary: The genetic characterization of a growing number of monogenic autoinflammatory diseases has provided important insights into the phenotypic expression of single gene disorders and the complexity of the dysregulated inflammatory pathways leading to clinical disease. Knowledge obtained from these disorders is pertinent to a number of common disorders and provides new targets for drug development.

AB - Purpose Of Review: The genetic and clinical characterizations of monogenic autoinflammatory syndromes have led to ground breaking insights into the regulation of inflammatory responses to endogenous and exogenous inducers or triggers of inflammation and continue to uncover key inflammatory pathways of the innate immune system. This article summarizes recent progress in the clinical aspects and understanding of the pathogenesis of this growing spectrum of diseases. Recent Findings: The understanding of the spectrum of organ manifestations in autoinflammation was expanded by the discovery of two novel monogenic diseases both caused by the absence of an anti-inflammatory signal and added evidence that increased IL-1 signaling can cause aseptic osteolytic bone lesions and that the absence of IL-10 signaling causes inflammatory enterocolitis in neonates. New knock in animal models for TNF-receptor- associated periodic syndrome, and familial Mediterranean fever and cryopyrin-associated periodic syndromes allow insights into the complexity of the dysregulated immune pathways. Exploring 'triggers' of the NLRP3 inflammasome spurred studies of tissue inflammation in diseases including gout and those that previously have not been considered inflammatory in nature such as diabetes, fibrosing lung disease and possibly coronary artery disease. Summary: The genetic characterization of a growing number of monogenic autoinflammatory diseases has provided important insights into the phenotypic expression of single gene disorders and the complexity of the dysregulated inflammatory pathways leading to clinical disease. Knowledge obtained from these disorders is pertinent to a number of common disorders and provides new targets for drug development.

KW - autoinflammatory diseases

KW - cryopyrin-associated periodic syndromes

KW - deficiency of the IL-1 receptor antagonist

KW - familial Mediterranean fever

KW - hyperimmunoglobulinemia D with periodic fevers syndrome

KW - IL-1

KW - inflammasome

KW - TNF-receptor-associated periodic syndrome

UR - http://www.scopus.com/inward/record.url?scp=77955162922&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955162922&partnerID=8YFLogxK

U2 - 10.1097/BOR.0b013e32833ceff4

DO - 10.1097/BOR.0b013e32833ceff4

M3 - Review article

C2 - 20671522

AN - SCOPUS:77955162922

VL - 22

SP - 567

EP - 578

JO - Current Opinion in Rheumatology

JF - Current Opinion in Rheumatology

SN - 1040-8711

IS - 5

ER -