Skip to main content
SpringerLink
Log in

Autoinflammatorische Erkrankungen – ein expandierendes Spektrum

Autoinflammatory diseases—An expanding spectrum

  • Leitthema
  • Published:
Monatsschrift Kinderheilkunde Aims and scope Submit manuscript

Zusammenfassung

Autoinflammatorische Erkrankungen umfassen eine immer größer werdende, genetisch heterogene Gruppe von Erkrankungen mit breitem und variablem klinischen Spektrum. Aus nosologischer Perspektive wird eine strikte Abgrenzung der Autoinflammation von Autoimmunität und Immundefizienz dem aktuellen Kenntnisstand zu pathogenetischen Mechanismen nicht gerecht. Daher erscheint eine systembasierte Einteilung, die sich an den in die inflammatorischen Prozesse involvierten Signalwegen orientiert, auch im Hinblick auf das klinische Management sinnvoll. So sprechen die Inflammasomopathien in vielen Fällen auf eine Blockade des Interleukin(IL)-1β an, während die Typ-1-Interferonopathien einer Therapie mithilfe der Januskinase(JAK)-Inhibition zugänglich sind.

Abstract

Autoinflammatory diseases comprise a growing genetically heterogeneous group of diseases with a broad and variable clinical spectrum. From a nosological perspective, a strict demarcation of autoinflammation from autoimmunity and immunodeficiency does not reflect the current state of knowledge on pathogenetic mechanisms. Therefore, a system-based classification according to the signalling pathways involved in the inflammatory processes, appears to be more useful also with respect to clinical management. As such, inflammasomopathies commonly respond to an interleukin 1 beta (IL-1-beta) blockade, while type 1 interferonopathies can be treated with Janus kinase (JAK) inhibition.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Literatur

  1. Agarwal AK, Xing C, DeMartino GN et al (2010) PSMB8 encoding the β5i proteasome subunit is mutated in joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy syndrome. Am J Hum Genet 87:866–872. https://doi.org/10.1016/j.ajhg.2010.10.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Aicardi J, Goutieres F (1984) A progressive familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis. Ann Neurol 15:49–54

    Article  CAS  Google Scholar 

  3. Bienias M, Brück N, Griep C et al (2018) Therapeutic Approaches to Type I Interferonopathies. Curr Rheumatol Rep 20:32. https://doi.org/10.1007/s11926-018-0743-3

    Article  CAS  PubMed  Google Scholar 

  4. Brehm A, Liu Y, Sheikh A et al (2015) Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production. J Clin Invest 125:4196–4211. https://doi.org/10.1172/JCI81260

    Article  PubMed  PubMed Central  Google Scholar 

  5. Canna SW, de Jesus AA, Gouni S et al (2014) An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat Genet 46:1140–1146. https://doi.org/10.1038/ng.3089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Crow YJ, Stetson DB (2021) The type I interferonopathies: 10 years on. Nat Rev Immunol. https://doi.org/10.1038/s41577-021-00633-9

    Article  PubMed  PubMed Central  Google Scholar 

  7. Duewell P, Kono H, Rayner KJ et al (2010) NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464:1357–1361. https://doi.org/10.1038/nature08938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Grandemange S, Sanchez E, Louis-Plence P et al (2017) A new autoinflammatory and autoimmune syndrome associated with NLRP1 mutations: NAIAD (NLRP1-associated autoinflammation with arthritis and dyskeratosis). Ann Rheum Dis 76:1191–1198. https://doi.org/10.1136/annrheumdis-2016-210021

    Article  CAS  PubMed  Google Scholar 

  9. Jeremiah N, Neven B, Gentili M et al (2014) Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations. J Clin Invest 124:5516–5520

    Article  Google Scholar 

  10. Kitamura A, Sasaki Y, Abe T et al (2014) An inherited mutation in NLRC4 causes autoinflammation in human and mice. J Exp Med 211:2385–2396. https://doi.org/10.1084/jem.20141091

    Article  PubMed  PubMed Central  Google Scholar 

  11. König N, Fiehn C, Wolf C et al (2017) Familial chilblain lupus due to a gain-of-function mutation in STING. Ann Rheum Dis 76:468–472. https://doi.org/10.1136/annrheumdis-2016-209841

    Article  CAS  PubMed  Google Scholar 

  12. Lee-Kirsch MA (2017) The type I interferonopathies. Annu Rev Med 68:297–315. https://doi.org/10.1146/annurev-med-050715-104506

    Article  CAS  PubMed  Google Scholar 

  13. Liu Y, Jesus AA, Marrero B et al (2014) Activated STING in a vascular and pulmonary syndrome. N Engl J Med 371:507–518

    Article  CAS  Google Scholar 

  14. Liu Y, Ramot Y, Torrelo A et al (2012) Mutations in proteasome subunit beta type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity. Arthritis Rheum 64:895–907

    Article  CAS  Google Scholar 

  15. Louvrier C, Assrawi E, El Khouri E et al (2020) NLRP3-associated autoinflammatory diseases: phenotypic and molecular characteristics of germline versus somatic mutations. J Allergy Clin Immunol 145:1254–1261. https://doi.org/10.1016/j.jaci.2019.11.035

    Article  CAS  PubMed  Google Scholar 

  16. Manthiram K, Zhou Q, Aksentijevich I, Kastner DL (2017) The monogenic autoinflammatory diseases define new pathways in human innate immunity and inflammation. Nat Immunol 18:832–842. https://doi.org/10.1038/ni.3777

    Article  CAS  PubMed  Google Scholar 

  17. Martinon F, Pétrilli V, Mayor A et al (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440:237–241. https://doi.org/10.1038/nature04516

    Article  CAS  PubMed  Google Scholar 

  18. McDermott MF, Aksentijevich I, Galon J et al (1999) Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell 97:133–144

    Article  CAS  Google Scholar 

  19. Mensa-Vilaró A, Bravo García-Morato M, de la Calle-Martin O et al (2019) Unexpected relevant role of gene mosaicism in patients with primary immunodeficiency diseases. J Allergy Clin Immunol 143:359–368. https://doi.org/10.1016/j.jaci.2018.09.009

    Article  CAS  PubMed  Google Scholar 

  20. Rathinam VAK, Vanaja SK, Fitzgerald KA (2012) Regulation of inflammasome signaling. Nat Immunol 13:333–342. https://doi.org/10.1038/ni.2237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Romberg N, Al Moussawi K, Nelson-Williams C et al (2014) Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation. Nat Genet 46:1135–1139. https://doi.org/10.1038/ng.3066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sanchez GAM, Reinhardt A, Ramsey S et al (2018) JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies. J Clin Invest 128:3041–3052. https://doi.org/10.1172/JCI98814

    Article  PubMed  PubMed Central  Google Scholar 

  23. Savic S, Caseley EA, McDermott MF (2020) Moving towards a systems-based classification of innate immune-mediated diseases. Nat Rev Rheumatol 16:222–237. https://doi.org/10.1038/s41584-020-0377-5

    Article  PubMed  Google Scholar 

  24. Schroder K, Zhou R, Tschopp J (2010) The NLRP3 inflammasome: a sensor for metabolic danger? Science 327:296–300. https://doi.org/10.1126/science.1184003

    Article  CAS  PubMed  Google Scholar 

  25. Vanderver A, Adang L, Gavazzi F et al (2020) Janus kinase inhibition in the Aicardi-Goutières syndrome. N Engl J Med 383:986–989. https://doi.org/10.1056/NEJMc2001362

    Article  PubMed  PubMed Central  Google Scholar 

  26. Wang L, Wen W, Deng M et al (2021) A novel mutation in the NBD domain of NLRC4 causes mild autoinflammation with recurrent urticaria. Front Immunol 12:674808. https://doi.org/10.3389/fimmu.2021.674808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik für Kinder- und Jugendmedizin, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Deutschland

    Sophia Weidler &  Min Ae Lee-Kirsch

  2. Molekulare Pädiatrie, Klinik für Kinder- und Jugendmedizin, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Deutschland

    Sophia Weidler

Authors
  1. Sophia Weidler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Min Ae Lee-Kirsch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Sophia Weidler or Min Ae Lee-Kirsch.

Ethics declarations

Interessenkonflikt

S. Weidler und M.A. Lee-Kirsch geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autorinnen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Additional information

Redaktion

Gesine Hansen, Hannover

figure qr

QR-Code scannen & Beitrag online lesen

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Weidler, S., Lee-Kirsch, M.A. Autoinflammatorische Erkrankungen – ein expandierendes Spektrum. Monatsschr Kinderheilkd 170, 335–340 (2022). https://doi.org/10.1007/s00112-022-01436-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00112-022-01436-5

Schlüsselwörter

Keywords

Search

Navigation