Toward a better understanding of type I interferonopathies: a brief summary, update and beyond

World J Pediatr. 2020 Feb;16(1):44-51. doi: 10.1007/s12519-019-00273-z. Epub 2019 Aug 3.

Abstract

Backgrounds: Type I interferonopathy is a group of autoinflammatory disorders associated with prominent enhanced type I interferon signaling. The mechanisms are complex, and the clinical phenotypes are diverse. This review briefly summarized the recent progresses of type I interferonopathy focusing on the clinical and molecular features, pathogeneses, diagnoses and potential therapies.

Data sources: Original research articles and literature reviews published in PubMed-indexed journals.

Results: Type I interferonopathies include Aicardi-Goutières syndrome, spondyloenchondro-dysplasia with immune dysregulation, stimulator of interferon genes-associated vasculopathy with onset in infancy, X-linked reticulate pigmentary disorder, ubiquitin-specific peptidase 18 deficiency, chronic atypical neutrophilic dermatitis with lipodystrophy, and Singleton-Merten syndrome originally. Other disorders including interferon-stimulated gene 15 deficiency and DNAse II deficiency are believed to be interferonopathies as well. Intracranial calcification, skin vasculopathy, interstitial lung disease, failure to thrive, skeletal development problems and autoimmune features are common. Abnormal responses to nucleic acid stimuli and defective regulation of protein degradation are main mechanisms in disease pathogenesis. First generation Janus kinase inhibitors including baricitinib, tofacitinib and ruxolitinib are useful for disease control. Reverse transcriptase inhibitors seem to be another option for Aicardi-Goutières syndrome.

Conclusions: Tremendous progress has been made for the discovery of type I interferonopathies and responsible genes. Janus kinase inhibitors and other agents have potential therapeutic roles. Future basic, translational and clinical studies towards disease monitoring and powerful therapies are warranted.

Keywords: Hereditary autoinflammatory diseases; Interferon type I; Janus kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Aortic Diseases / drug therapy
  • Aortic Diseases / genetics
  • Aortic Diseases / immunology
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases of the Nervous System / drug therapy
  • Autoimmune Diseases of the Nervous System / genetics
  • Autoimmune Diseases of the Nervous System / immunology
  • Child
  • Dental Enamel Hypoplasia / drug therapy
  • Dental Enamel Hypoplasia / genetics
  • Dental Enamel Hypoplasia / immunology
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Interferon Type I / genetics
  • Interferon Type I / immunology*
  • Metacarpus / abnormalities
  • Metacarpus / immunology
  • Muscular Diseases / drug therapy
  • Muscular Diseases / genetics
  • Muscular Diseases / immunology
  • Nervous System Malformations / drug therapy
  • Nervous System Malformations / genetics
  • Nervous System Malformations / immunology
  • Odontodysplasia / drug therapy
  • Odontodysplasia / genetics
  • Odontodysplasia / immunology
  • Osteoporosis / drug therapy
  • Osteoporosis / genetics
  • Osteoporosis / immunology
  • Phenotype
  • Protein Kinase Inhibitors / therapeutic use
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Vascular Calcification / drug therapy
  • Vascular Calcification / genetics
  • Vascular Calcification / immunology

Substances

  • Immunosuppressive Agents
  • Interferon Type I
  • Protein Kinase Inhibitors
  • Reverse Transcriptase Inhibitors

Supplementary concepts

  • Aicardi-Goutieres syndrome
  • Singleton Merten syndrome