Encyclopedia of Medical Immunology

Living Edition
| Editors: Ian MacKay, Noel R. Rose

Introduction to Autoinflammatory Diseases

  • Raphaela Goldbach-ManskyEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-9209-2_116-1

Definition of Autoinflammatory Diseases

Autoinflammatory diseases are genetically defined immune-dysregulatory conditions that typically present in early childhood with systemic inflammation (i.e., fever, rashes) and with disease-specific sterile organ inflammation, with the recruitment of a predominantly innate immune cell infiltrate in affected tissues. Most mutations that cause autoinflammatory diseases affect key innate immune sensor pathways that lead to cytokine dysregulation including IL-1, type 1 IFN, IL-18, and IL-17 and, more generally, increased NFκB signaling.


The term “autoinflammatory diseases” was introduced in 1999 in a seminal paper by Drs. Michael McDermott and Daniel Kastner et al. that reported the genetic cause for the tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) (McDermott et al. 1999). This concept aimed to distinguish familial Mediterranean fever (FMF) and TRAPS, the then only genetically defined “periodic fever...

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  1. Broderick L, De Nardo D, Franklin BS, Hoffman HM, Latz E. The inflammasomes and autoinflammatory syndromes. Annu Rev Pathol. 2015;10:395–424.CrossRefGoogle Scholar
  2. Cox AJ, Ferguson PJ. Update on the genetics of nonbacterial osteomyelitis in humans. Curr Opin Rheumatol. 2018;30(5):521–5.PubMedGoogle Scholar
  3. de Jesus AA, Canna SW, Liu Y, Goldbach-Mansky R. Molecular mechanisms in genetically defined autoinflammatory diseases: disorders of amplified danger signaling. Annu Rev Immunol. 2015;33:823–74.CrossRefGoogle Scholar
  4. Jesus AA, Goldbach-Mansky R. IL-1 blockade in autoinflammatory syndromes. Annu Rev Med. 2014;65:223–44.CrossRefGoogle Scholar
  5. Kim H, Sanchez GA, Goldbach-Mansky R. Insights from Mendelian Interferonopathies: comparison of CANDLE, SAVI with AGS monogenic lupus. J Mol Med (Berl). 2016;94(10):1111–27.CrossRefGoogle Scholar
  6. Manthiram K, Zhou Q, Aksentijevich I, Kastner DL. The monogenic autoinflammatory diseases define new pathways in human innate immunity and inflammation. Nat Immunol. 2017;18(8):832–42.CrossRefGoogle Scholar
  7. McDermott MF, Aksentijevich I, Galon J, McDermott EM, Ogunkolade BW, Centola M, et al. Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell. 1999;97(1):133–44.CrossRefGoogle Scholar
  8. Rodero MP, Crow YJ. Type I interferon-mediated monogenic autoinflammation: the type I interferonopathies. A conceptual overview. J Exp Med. 2016;213(12):2527–38.CrossRefGoogle Scholar

Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2018

Authors and Affiliations

  1. 1.Translational Autoinflammatory Diseases Section (TADS)National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)BethesdaUSA

Section editors and affiliations

  • Raphaela Goldbach-Mansky
    • 1
  1. 1.NIAID, Translational Autoinflammatory Disease StudiesNational Institutes of Health Clinical CenterBethesdaUSA