Clinical spectrum and currently available treatment of type I interferonopathy Aicardi-Goutières syndrome.

Aicardi–Goutières syndrome Immunosuppressive drugs Interferon-α Neuroinflammation Systemic lupus erythematosus

Journal

World journal of pediatrics : WJP
ISSN: 1867-0687
Titre abrégé: World J Pediatr
Pays: Switzerland
ID NLM: 101278599

Informations de publication

Date de publication:
Jul 2023
Historique:
received: 25 04 2022
accepted: 22 12 2022
medline: 13 6 2023
pubmed: 18 1 2023
entrez: 17 1 2023
Statut: ppublish

Résumé

Aicardi-Goutières syndrome (AGS) is a genetically determined disorder with a variable phenotype. Since the original description of AGS, advances in gene sequencing techniques have resulted in a significant broadening of the phenotypic spectrum associated with AGS genes, and new clinical pictures have emerged beyond the classic presentation. The aim of this review is to provide a comprehensive analysis of the clinical spectrum of AGS and report currently available treatments and new immunosuppressive strategies. Literature reviews and original research articles were collected from databases, including PubMed and ClinicalTrials.gov. Relevant articles about AGS were included. The involvement of the nervous system certainly represents the major cause of mortality and morbidity in AGS patients. However, other clinical manifestations, such as chilblains, hepatosplenomegaly, and hematological disturbances, may lead to the diagnosis and considerably impact the prognosis and overall quality of life of these patients. Therapeutic approaches of AGS are limited to interventions aimed at specific symptoms and the management of multiple comorbidities. However, advances in understanding the pathogenesis of AGS could open new and more effective therapies. The over-activation of innate immunity due to upregulated interferon production plays a critical role in AGS, leading to multi-organ damage with the main involvement of the central nervous system. To date, there is no specific and effective treatment for AGS. New drugs specifically targeting the interferon pathway may bring new hope to AGS patients.

Sections du résumé

BACKGROUND BACKGROUND
Aicardi-Goutières syndrome (AGS) is a genetically determined disorder with a variable phenotype. Since the original description of AGS, advances in gene sequencing techniques have resulted in a significant broadening of the phenotypic spectrum associated with AGS genes, and new clinical pictures have emerged beyond the classic presentation. The aim of this review is to provide a comprehensive analysis of the clinical spectrum of AGS and report currently available treatments and new immunosuppressive strategies.
DATA SOURCES METHODS
Literature reviews and original research articles were collected from databases, including PubMed and ClinicalTrials.gov. Relevant articles about AGS were included.
RESULTS RESULTS
The involvement of the nervous system certainly represents the major cause of mortality and morbidity in AGS patients. However, other clinical manifestations, such as chilblains, hepatosplenomegaly, and hematological disturbances, may lead to the diagnosis and considerably impact the prognosis and overall quality of life of these patients. Therapeutic approaches of AGS are limited to interventions aimed at specific symptoms and the management of multiple comorbidities. However, advances in understanding the pathogenesis of AGS could open new and more effective therapies.
CONCLUSIONS CONCLUSIONS
The over-activation of innate immunity due to upregulated interferon production plays a critical role in AGS, leading to multi-organ damage with the main involvement of the central nervous system. To date, there is no specific and effective treatment for AGS. New drugs specifically targeting the interferon pathway may bring new hope to AGS patients.

Identifiants

pubmed: 36650407
doi: 10.1007/s12519-022-00679-2
pii: 10.1007/s12519-022-00679-2
pmc: PMC10258176
doi:

Substances chimiques

Interferons 9008-11-1

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

635-643

Informations de copyright

© 2023. The Author(s).

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Auteurs

Giovanni Battista Dell'Isola (GB)

Department of Pediatrics, University of Perugia, Giorgio Menghini Square, 06129, Perugia, Italy. giovanni.dellisola@gmail.com.

Gianluca Dini (G)

Department of Pediatrics, University of Perugia, Giorgio Menghini Square, 06129, Perugia, Italy.

Kaleb Logan Culpepper (KL)

Department of Neurology Jacksonville, University of Florida, Florida, USA.

Katherin Elizabeth Portwood (KE)

Department of Pediatrics, Division of Child Neurology, University of Florida, UF Health Shands Children's Hospital, Gainesville, FL, USA.

Pietro Ferrara (P)

Unit of Pediatrics, Campus Bio-Medico University, Rome, Italy.

Giuseppe Di Cara (G)

Department of Pediatrics, University of Perugia, Giorgio Menghini Square, 06129, Perugia, Italy.

Alberto Verrotti (A)

Department of Pediatrics, University of Perugia, Giorgio Menghini Square, 06129, Perugia, Italy.

Mauro Lodolo (M)

Department of Pediatrics, Division of Child Neurology, University of Florida, UF Health Shands Children's Hospital, Gainesville, FL, USA.

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