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hereditary autoinflammatory diseases

Tuesday 14 June 2005

Definition: Autoinflammatory diseases are defined as recurrent "unprovoked" inflammatory events which do not produce high-titer autoantibodies or antigen-specific T cells.

The autoinflammatory disorders are a new and expanding classification of inflammatory diseases characterized by recurrent episodes of systemic inflammation in the absence of pathogens, autoantibodies or antigen specific T cells.

These disorders are caused by primary dysfunction of the innate immune system, without evidence of adaptive immune dysregulation.

Innate immune abnormalities include aberrant responses to pathogen associated molecular patterns (PAMPs) like lipopolysaccharide and peptidoglycan, prominent neutrophilia in blood and tissues, and dysregulation of inflammatory cytokines (IL-1beta, TNF-alpha) or their receptors.

The hereditary autoinflammatory diseases arise from mutations of genes regulating the innate immune system. These rare disorders are well characterized, both clinically and in terms of their molecular pathogenesis.

The recurrent attacks of febrile polyserositis of Familial Mediterranean Fever (FMF) are due to defective pyrin, a protein that down-regulates inflammation.

The Hyperimmunoglobulinemia D Syndrome (HIDS), which mimics FMF, results from a genetically conferred deficiency of mevalonate kinase.

TRAPS (TNF Receptor Associated Periodic Syndrome), formerly known as Familial Hibernian Fever, is caused by a defective membrane receptor for TNF.

Three other hereditary disorders which overlap in their clinical expression - Familial Cold Autoinflammatory Syndrome, the Muckle Wells syndrome, and Neonatal Onset Multisystem Inflamatory Disease (NOMID) - are a consequence of gain-of-function mutations of the gene encoding cryopyrin, the scaffolding protein of the inflammasome.

The PAPA syndrome (Pyogenic Arthritis, Pyoderma gangrenosum, Acne) results from mutations of a gene that increases the binding of its product (PSPSTPIP1) to pyrin, thereby blunting the inhibitory effect of pyrin on inflammasome activation.

Types

- Familial Mediterranean fever (FMF)
- mevalonate kinase deficiency (MKD)
- hyperimmunoglobulinemia D with periodic fever syndrome (HIDS)
- tumor necrosis factor receptor-associated periodic syndrome (TRAPS)
- cryopyrin-associated periodic syndrome (CAPS)
- Pyogenic sterile Arthritis, Pyoderma gangrenosum and Acne syndrome, (PAPA syndrome)
- chronic recurrent multifocal osteomyelitis (CRMO)
- familial juvenile systemic granulomatosis (Blau syndrome)
- Muckle-Wells syndrome (MWS)
- familial cold autoinflammatory syndrome (FCAS)
- chronic infantile neurologic cutaneous articular (CINCA) syndrome or neonatal-onset multisystem inflammatory disease (NOMID)
- pyogenic sterile arthritis
- pyoderma gangrenosum
- acne (PAPA)
- Crohn disease
- Behçet disease

Open References

- The autoinflammatory diseases. Federici S, Caorsi R, Gattorno M. Swiss Med Wkly. 2012 Jun 19;142:0. PMID: 22714396 (Free)

References

- Galeazzi M, Gasbarrini G, Ghirardello A, Grandemange S, Hoffman HM, Manna R, Podswiadek M, Punzi L, Sebastiani GD, Touitou I, Doria A. Autoinflammatory syndromes. Clin Exp Rheumatol. 2006 Jan-Feb;24(1 Suppl 40):S79-85. PMID: 16466630

- Tunca M, Ozdogan H. Molecular and genetic characteristics of hereditary autoinflammatory diseases. Curr Drug Targets Inflamm Allergy. 2005 Feb;4(1):77-80. PMID: 15720239

- Touitou I, Notarnicola C, Grandemange S. Identifying mutations in autoinflammatory diseases: towards novel genetic tests and therapies? Am J Pharmacogenomics. 2004;4(2):109-18. PMID: 15059033

- McDermott MF, Aksentijevich I. The autoinflammatory syndromes. Curr Opin Allergy Clin Immunol. 2002 Dec;2(6):511-6. PMID: 14752334

- Sohar E, et al. Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med. 1967;43:227.

- Dinarello CA, et al. Colchicine therapy for familial mediterranean fever. A double-blind trial. N Engl J Med. 1974;291:934.

- The International FMF Consortium. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell 1997. Aug 22;90(4):797–807.

- Simon A, et al. Molecular analysis of the mevalonate kinase gene in a cohort of patients with the hyper-Igd and periodic fever syndrome: its application as a diagnostic tool. Ann Intern Med. 2001 Sep 4;135(5):338–43.

- Drenth JP, et al. Hyperimmunoglobulinemia D and periodic fever syndrome. The clinical spectrum in a series of 50 patients. International Hyper-IgD Study Group. Medicine (Baltimore). 1994 May;73(3):133–44.

- Hull KM, et al. The TNF receptor-associated periodic syndrome (TRAPS): emerging concepts of an autoinflammatory disorder. Medicine (Baltimore). 2002 Sep;81(5):349–68.

- Aksentijevich I, et al. The clinical continuum of cryopyrinopathies: Novel CIAS1 mutations in North American patients and a new cryopyrin model. Arthritis Rheum. 2007 Mar 28;56(4):1273– 1285.

- Prieur AM. Quartier dit Maire P Cryopyrinopathies: update on pathogenesis and treatment. Nat Clin Pract Rheumatol. 2008 Sep;4(9):481–9.

- Doeglas HM, Bleumink E. Familial cold urticaria. Clinical findings. Arch Dermatol. 1974;110:382.

- Muckle TJ, Wells M. Urticaria, deafness, and amyloidosis: a new heredo-familial syndrome. Q J Med. 1962;31:235.

- Hawkins PN, et al. Spectrum of clinical features in Muckle-Wells syndrome and response to anakinra. Arthritis Rheum. 2004 Feb;50(2):607–12.

- Prieur AM. A recently recognised chronic inflammatory disease of early onset characterized by the triad of rash, central nervous system involvement and arthropathy. Clin Exp Rheumatol. 2001 Jan–Feb;19(1):103–6.

- Lindor NM, et al. A new autosomal dominant disorder of pyogenic sterile arthritis, pyoderma gangrenosum, and acne: PAPA syndrome. Mayo Clin Proc. 1997 Jul;72(7):611–5.