Skip to main content
SpringerLink
Log in

Autoinflammatorische Syndrome

Autoinflammatory syndromes

  • Schwerpunkt: Fieber unklarer Genese
  • Published:
Der Internist Aims and scope Submit manuscript

Zusammenfassung

Unter dem Begriff „autoinflammatorische Syndrome“ werden hereditäre periodische Fiebersyndrome (HPF) verstanden, die durch Mutationen von Mustererkennungsrezeptoren („pattern-recognition receptors“, PRR) und Störungen der Zytokingeneration und -balance hervorgerufen werden. Zu ihnen zählen die Cyropyrinopathien, das familiäre Mittelmeerfieber, das TNF-Rezeptor-assoziierte periodische Fiebersyndrom (TRAPS), das Hyper-IgD- und periodisches Fieber-Syndrom (HIDS), die pyogene sterile Arthritis, das Pyoderma-gangraenosum- und Akne- (PAPA-) Syndrom, das NALP12-HPF und das Blau-Syndrom. Pathophysiologisches Kennzeichen ist eine spontane Aktivierung von Zellen der angeborenen Immunität in Abwesenheit von Liganden. Autoantikörper sind in der Regel nicht nachweisbar. Klinisch sind HPF durch rezidivierende Fieberepisoden und Entzündung, insbesondere seröser und synovialer Grenzflächen sowie der Haut gekennzeichnet. Interessanterweise spielen PRR-vermittelte, autoinflammatorische Vorgänge auch bei verschiedenen chronisch-entzündlichen und autoimmunen Erkrankungen eine Rolle.

Abstract

In its strict sense, the term “autoinflammatory syndromes” comprises the hereditary periodic fever syndromes (HPF), which are caused by mutations of pattern-recognition receptors (PRR) and perturbations of the cytokine balance. These include the crypyrinopathies, familial Mediterranean fever, TNF-receptor associated periodic fever syndrome (TRAPS), hyper-IgD and periodic syndrome (HIDS), pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA) syndrome, NALP12-HPF, and the Blau syndrome. The diseases are characterized by spontaneous activation of cells of the innate immunity in the absence of ligands. Autoantibodies are usually not found. HPF clinically present with recurrent fever episodes and inflammation, especially of serosal and synovial interfaces and the skin. Intriguingly, PRR-mediated autoinflammtory mechanisms also play a role in a number of chronic inflammatory and autoimmune diseases.

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

Abb. 1

Abbreviations

ASC:

Apoptosis associated speck-like protein with a caspase recruitment Domain

CINCA:

Chronic infantile neurological cutaneous and articular syndrome

DAMP:

Danger-assoziiertes molekulares Muster

FCAS:

Familial cold autoinflammatory syndrome

FMF:

Familiäres Mittelmeerfieber

HIDS:

Hyper-IgD- und periodisches Fieber-Syndrom (HIDS)

IL:

Interleukin

INF:

Interferon

MWS:

Muckle-Wells-Syndrom

NALP:

NACHT-, LRR- and pyrin-domain-containing protein

NLR:

NOD-like-Rezeptor

NLRP:

Nucleoitid-binding oligomerization-domain protein (NOD)-like receptor family, pyrin domain containing

NOD:

Nucleoitid-binding oligomerization-domain protein

NOMID:

Neonatal-onset multisystem inflammatory disease

PAMP:

Pathogenassoziiertes molekulares Muster (PAMP)

PAPA:

Pyogene sterile Arthritis, Pyoderma-gangraenosum- und Akne-Syndrom

PRR:

Pattern-recognition receptor, Mustererkenungsrezeptor

SAA:

Serumamyloid A

TLR:

Toll-like-Rezeptor

TNF:

Tumornekrosefaktor

TRAPS:

TNF-Rezeptor-assoziiertes periodisches Syndrom

Literatur

  1. Chae JJ, Wood G, Masters SL et al (2006) The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1β production. Proc Natl Acad Sci U S A 103:9982–9987

    Article  PubMed  CAS  Google Scholar 

  2. Church LD, McDermott MF (2009) Canakinumab, a fully-human mAb against IL-1beta for the potential treatment of inflammatory disorders. Curr Opin Mol Ther 11:81–89

    PubMed  CAS  Google Scholar 

  3. Daysal S, Akcil G, Goker B et al (2005) Infiximab therapy in a patient with familial Mediterranean fever and chronic hip arthritis. Arthritis Rheum 53:146–148

    Article  PubMed  Google Scholar 

  4. Delpech M, Grateau G (2001) Genetically determined recurrent fevers. Curr Opin Immunol 13:539–542

    Article  PubMed  CAS  Google Scholar 

  5. Dinarello CA, Wolff SM, Goldfinger SE et al (1974) Colchicine therapy for familial Mediterranean fever: A double-blind trial. N Engl J Med 291:934–937

    Article  PubMed  CAS  Google Scholar 

  6. Drenth JPH, van der Meer JWM (2001) Hereditary periodic fever. New Engl J Med 345:1748–1757

    Article  PubMed  CAS  Google Scholar 

  7. Drewe E, McDermott EM, Powell RJ (2000) Treatment of the nephrotic syndrome with etanercept in patients with the tumor necrosis factor receptor-associated periodic syndrome. N Engl J Med 343:1044–1045

    Article  PubMed  CAS  Google Scholar 

  8. Goldbach-Mansky R, Dailey N, Canna S et al (2006) Neonatal-onset multisystem inflammatory disease responsive to interleukin-1β inhibition. New Engl J Med 355:581–592

    Article  PubMed  CAS  Google Scholar 

  9. Halle A, Horung V, Petzold GC et al (2008) The NALP3 inflammasome is involved in the innate immune response to amyloid-β. Nat Immunol 8:857–865

    Article  CAS  Google Scholar 

  10. Hoffman HM, Mueller JL, Broide DH et al (2001) Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammtory syndrome and Muckle-Wells syndrome. Nat Genet 29:301–305

    Article  PubMed  CAS  Google Scholar 

  11. Hoffman HM, Throne ML, Amar NJ et al (2008) Efficacy and safety of rilonacept (interleukin-1 trap) in patients with cryopyrin-associated periodic syndromes: Results from two sequential placebo-controlled studies. Arthritis Rheum 58:2443–2452

    Article  PubMed  CAS  Google Scholar 

  12. Holle JU, Capraru D, Csernok E et al (2006) Expansion of CD28-CD27-NKG2D+ effector memory T cells and predominant Th1-type response during febrile attacks in tumor necrosis factor-associated periodic syndrome. Isr Med Assoc J 8:142–144

    PubMed  Google Scholar 

  13. Jeru I, Duquesnoy P, Fernandes-Alnemri T et al (2008) Mutations in NALP12 cause hereditary periodic fever syndromes. Proc Natl Acad Sci 105:1614–1619

    Article  PubMed  CAS  Google Scholar 

  14. Lamprecht P, Timmann C, Ahmadi-Simab K, Gross WL (2004) Hereditäres periodisches Fieber. Internist 45:904–911

    Article  PubMed  CAS  Google Scholar 

  15. Lamprecht P, Moosig F, Adam-Klages S et al (2004) Small vessel vasculitis and replapsing panniculitis in tumour necrosis factor asscoiated periodic syndrome (TRAPS). Ann Rheum Dis 63:1518–1520

    Article  PubMed  CAS  Google Scholar 

  16. Lamprecht P, Till A, Kabelitz D (2008) New aspects of the pathogenesis of gout. Danger signals, autoinflammation and beyond. Z Rheumatol 67:151–156

    Article  PubMed  CAS  Google Scholar 

  17. Livneh A, Langewitz P, Shinar Y et al (1999) MEFV mutation analysis in patients suffering from amyloidosis of familial Mediterranean fever. Amyloid 6:1–6

    PubMed  CAS  Google Scholar 

  18. Lobito AA, Kimberley FC, Muppidi JR et al (2006) Abnormal disulfide-linked oligomerization results in ER retention and altered siganling by TNFR1 mutants in TNFR1-associated periodic fever syndrome (TRAPS). Blood 108:1320–1327

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  20. Nedjai B, Hitman GA, Yousaf N et al (2008) Abnormal tumor necrosis factor I cell surface expression and NF-kappaB activation in tumor necrosis factor receptor-associated peridoc syndrome. Arthritis Rheum 58:273–283

    Article  PubMed  CAS  Google Scholar 

  21. Neven B, Prieur AM, Quartier dit Maire P (2008) Cyropyrinopathies: Update on pathogenesis and treatment. Nat Clin Pract Rheumatol 4:481–489

    Article  PubMed  CAS  Google Scholar 

  22. Petrilli V, Dostert C, Muruve DA, Tschopp J (2007) The inflammasome: A danger sensing complex triggering innate immunity. Curr Opin Immunol 19:615–622

    Article  PubMed  CAS  Google Scholar 

  23. Ravet N, Rouaghe S, Dode C et al (2006) Clinical significance of P46L and R92Q substitutions in the tumor necrosis factor superfamily 1A gene. Ann Rheum Dis 65:1158–1162

    Article  PubMed  CAS  Google Scholar 

  24. Rebelo SL, Bainbridge SE, Amel-Kashipaz MR et al (2006) Modeling of tumor necrosis factor superfamily 1A mutants associated with tumor necrosis factor receptor-associated peridoc syndrome indicates misfolding consistent with abnormal function. Arthritis Rheum 54:2674–2687

    Article  PubMed  CAS  Google Scholar 

  25. Rebelo SL, Amel-Kashipaz MR, Radford PM et al (2009) Noevel markers of inflammation identified in tumor necrosis factor receptor-associated peridoc syndrome (TRAPS) in transcriptomic analysis of effects of TRAPS-associated tumor necrosis factor receptor type I mutants in an endothelial cell line. Arthritis Rheum 60:269–280

    Article  PubMed  CAS  Google Scholar 

  26. Samuels J, Ozen S (2006) Familial Mediterranean fever and the other autoinflammtory syndromes: Evaluation of the patient with recurrent fever. Curr Opin Rheumatol 18:108–117

    Article  PubMed  Google Scholar 

  27. Shinar Y, Livneh A, Langevitz P et al (2000) Genotype-phenotype assessment of common genotypes among patients with familial Mediterranean fever. J Rheumatol 27:1703–1707

    PubMed  CAS  Google Scholar 

  28. Shoham NG, Centola M, Mansfield E et al (2003) Pyrin binds the PSTPIP1 / CD“BP1 protein, defining familial Mediterranean fever and PAPA sindrome as disorders in the same pathway. Proc Natl Acad Sci U S A 100:13501–13506

    Article  PubMed  CAS  Google Scholar 

  29. The International FMF Consortium (1997) Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell 90:797–807

    Article  Google Scholar 

  30. Tunca M, Akar S, Soyturk M et al (2004) The effect of interferon alpha administration on acute attacks of familial Mediterranean fever: A double-blind, placebo controlled trial. Clin Exp Rheumatol 22(4 Suppl 34):S37–S40

    PubMed  CAS  Google Scholar 

Download references

Danksagung

Unser Dank gilt der DFG für die Unterstützung durch die Klinische Forschergruppe (KFO)170 „Frühpathogenese der Wegenerschen Granulomatose: Von der natürlichen Abwehr mit Granulombildung zur Autoimmunität“ und dem Exzellenzcluster „Inflammation at Interfaces“ Research Area E und JRG I-h.

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. Poliklinik für Rheumatologie, Vaskulitiszentrum UKSH & Klinikum Bad Bramstedt, Universität zu Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Deutschland

    P. Lamprecht & W.L. Gross

Authors
  1. P. Lamprecht
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W.L. Gross
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. Lamprecht.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lamprecht, P., Gross, W. Autoinflammatorische Syndrome. Internist 50, 676–684 (2009). https://doi.org/10.1007/s00108-009-2302-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00108-009-2302-5

Schlüsselwörter

Keywords

Search

Navigation