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Update on genetics and pathogenesis of autoinflammatory diseases: the last 2 years

Seminars in Immunopathology volume 37, pages 395–401 (2015)Cite this article

Abstract

Autoinflammatory diseases are a genetically heterogeneous group of rheumatologic diseases that are driven by abnormal activation of the innate immune system. Patients present with recurrent episodes of systemic inflammation and a spectrum of organ-specific comorbidities. These diseases are mediated by the overproduction of various inflammatory cytokines, such as IL-1, IL-18, IL-6, TNFα, and type I interferon. Treatments with biologic agents that inhibit these cytokines have been very efficient in most patients. During the past 2 years, remarkable progress has been made in the identification of disease-associated genes owing mostly to new technologies. Next generation sequencing technologies (NGS) have become instrumental in finding single-gene defects in undiagnosed patients with early onset symptoms. NGS has advanced the field of autoinflammation by identifying disease-causing genes that point to pathways not known to regulate cytokine signaling or inflammation. They include a protein that has a role in differentiation of myeloid cells, a ubiquitously expressed enzyme that catalyzes the addition of the CCA terminus to the 3-prime end of tRNA precursors, and an enzyme that catalyzes the oxidation of a broad range of substrates. Lastly, newly described mutations have informed a whole new dimension on genotype-phenotype relationships. Mutations in the same gene can give rise to a range of phenotypes with a common inflammatory component. This suggests greater than anticipated contributions by modifying alleles and environmental factors to disease expressivity.

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Authors and Affiliations

  1. Inflammatory Disease Section, National Human Genome Research Institute, Bldg. 10/Rm. B2-5235, 10 Center Drive - MSC 1849, Bethesda, MD, 20892-1849, USA

    Ivona Aksentijevich

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  1. Ivona Aksentijevich
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Correspondence to Ivona Aksentijevich.

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This article is a contribution to the Special Issue on The Inflammasome and Autoinflammatory Diseases - Guest Editors: Seth L. Masters, Tilmann Kallinich and Seza Ozen

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Cite this article

Aksentijevich, I. Update on genetics and pathogenesis of autoinflammatory diseases: the last 2 years. Semin Immunopathol 37, 395–401 (2015). https://doi.org/10.1007/s00281-015-0478-4

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  • DOI: https://doi.org/10.1007/s00281-015-0478-4

Keywords

  • Autoinflammation
  • Next generation sequencing (NGS)
  • Deficiency of ADA2 (DADA2)
  • STING-associated vasculopathy with onset in infancy (SAVI)
  • NLRC4-associated inflammatory diseases
  • TRNT1 deficiency/SIFD
  • LACC1-associated monogenic disease