Abstract
A new family of hereditary immunologic disorders known as the autoinflammatory diseases involves dysregulation of the innate immune system. Elucidation of the genetic basis of these disorders has resulted in improved understanding of the disease pathophysiology of systemic and tissue inflammation, and has also revealed novel nonpathologic innate immune mechanisms. These advances have also resulted in direct improvement in diagnosis and therapy for autoinflammatory disorders such as the cryopyrinopathies and familial Mediterranean fever and have implications for more common inflammatory diseases.
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References and Recommended Reading
Austen KF: Inborn and acquired abnormalities of the complement system of man. Johns Hopkins Med J 1971, 128:57–74.
Curnutte JT, Babior BM: Chronic granulomatous disease. Adv Hum Genet 1987, 16:229–297.
Conley ME: Primary immunodeficiencies: a flurry of new genes. Immunol Today 1995, 16:313–315.
Bonilla FA, Geha RS: 2. Update on primary immunodeficiency diseases. J Allergy Clin Immunol 2006, 117:S435–441.
Brydges S, Kastner DL: The systemic autoinflammatory diseases: inborn errors of the innate immune system. Curr Top Microbiol Immunol 2006, 305:127–160.
French FMF Consortium: A candidate gene for familial Mediterranean fever. The French FMF Consortium. Nat Genet 1997, 17:25–31.
International FMF Consortium: Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. The International FMF Consortium. Cell 1997, 90:797–807.
Hoffman HM, Mueller JL, Broide DH, et al.: Mutation of a new gene encoding a putative pyrin-like protein cause familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet 2001, 29:301–305.
Beutler B: The Toll-like receptors: analysis by forward genetic methods. Immunogenetics 2005, 57:385–392.
Medzhitov R, Preston-Hurlburt P, Janeway CA Jr: A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 1997, 388:394–397.
Harton JA, Linhoff MW, Zhang J, Ting JP: Cutting edge: CATERPILLER: a large family of mammalian genes containing CARD, pyrin, nucleotide-binding, and leucine-rich repeat domains. J Immunol 2002, 169:4088–4093.
Inohara N, Nunez G: NODs: intracellular proteins involved in inflammation and apoptosis. Nat Rev Immunol 2003, 3:371–382.
Tschopp J, Martinon F, Burns K: NALPs: a novel protein family involved in inflammation. Nat Rev Mol Cell Biol 2003, 4:95–104.
Bertin J, DiStefano PS: The PYRIN domain: a novel motif found in apoptosis and inflammation proteins. Cell Death Differ 2000, 7:1273–1274.
Ting JP, Kastner DL, Hoffman HM: CATERPILLERs, pyrin and hereditary immunological disorders. Nat Rev Immunol 2006, 6:183–195.
Ausubel FM: Are innate immune signaling pathways in plants and animals conserved? Nat Immunol 2005, 6:973–979.
Belkhadir Y, Subramaniam R, Dangl JL: Plant disease resistance protein signaling: NBS-LRR proteins and their partners. Curr Opin Plant Biol 2004, 7:391–399.
da Silva Correia J, Miranda Y, Leonard N, Ulevitch R: SGT1 is essential for Nod1 activation. Proc Natl Acad Sci U S A 2007.
Martinon F, Tschopp J: NLRs join TLRs as innate sensors of pathogens. Trends Immunol 2005, 26:447–454.
Ting JP, Trowsdale J: Genetic control of MHC class II expression. Cell 2002, 109(Suppl):S21–33.
Swanberg M, Lidman O, Padyukov L, et al.: MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction. Nat Genet 2005, 37:486–494.
Rosenstiel P, Till A, Schreiber S: NOD-like receptors and human diseases. Microbes and Infection 2007, In press.
Jin Y, Mailloux CM, Gowan K, et al.: NALP1 in vitiligo-associated multiple autoimmune disease. N Engl J Med 2007, 356, 1216–1225.
Hoffman HM, Gregory SG, Mueller JL, et al.: Fine structure mapping of CIAS1: identification of an ancestral haplotype and a common FCAS mutation, L353P. Hum Genet 2003, 112:209–216.
Hoffman HM, Wanderer AA, Broide DH: Familial cold autoinflammatory syndrome: phenotype and genotype of an autosomal dominant periodic fever. J Allergy Clin Immunol 2001, 108:615–620.
Muckle TJ: The ‘Muckle-Wells’ syndrome. Br J Dermatol 1979, 100:87–92.
Prieur AM, Griscelli C, Lampert F, et al.: A chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome. A specific entity analysed in 30 patients. Scand J Rheumatol Suppl 1987, 66:57–68.
Hawkins PN, Lachmann HJ, Aganna E, McDermott MF: Spectrum of clinical features in Muckle-Wells syndrome and response to anakinra. Arthritis Rheum 2004, 50:607–612.
Aksentijevich I, Nowak M, Mallah M, et al.: De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases. Arthritis Rheum 2002, 46:3340–3348.
Hentgen V, Despert V, Lepretre AC, et al.: Intrafamilial variable phenotypic expression of a CIAS1 mutation: from Muckle-Wells to chronic infantile neurological cutaneous and articular syndrome. J Rheumatol 2005, 32:747–751.
Feldmann J, Prieur AM, Quartier P, et al.: Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes. Am J Hum Genet 2002, 71:198–203.
Aksentijevich I, D Putnam C, Remmers EF, et al.: The clinical continuum of cryopyrinopathies: Novel CIAS1 mutations in North American patients and a new cryopyrin model. Arthritis Rheum 2007, 56:1273–1285.
Anderson JP, Mueller JL, Rosengren S, et al.: Structural, expression, and evolutionary analysis of mouse CIAS1. Gene 2004, 338:25–34.
Manji GA, Wang L, Geddes BJ, et al.: PYPAF1: A PYRIN-containing Apaf1-like protein that assembles with ASC and regulates activation of NF-kB. J Biol Chem 2002, 277:11570–11575.
Kummer JA, Broekhuizen R, Everett H, et al.: Inflammasome components NALP 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory response. J Histochem Cytochem 2007, 55:443–452.
Rosengren S, Hoffman HM, Bugbee W, Boyle DL: Expression and regulation of cryopyrin and related proteins in rheumatoid arthritis synovium. Ann Rheum Dis. 2005, 64:708–714.
Martinon F, Burns K, Tschopp J: The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 2002, 10:417–426.
Grahames CB, Michel AD, Chessell IP, Humphrey PP: Pharmacological characterization of ATP-and LPS-induced IL-1beta release in human monocytes. Br J Pharmacol 1999, 127:1915–1921.
Mariathasan S, Monack DM: Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation. Nat Rev Immunol 2007, 7:31–40.
Martinon F, Agostini L, Meylan E, Tschopp J: Identification of bacterial muramyl dipeptide as activator of the NALP3/cryopyrin inflammasome. Curr Biol 2004, 14:1929–1934.
Pan Q, Mathison J, Fearns C, et al.: MDP-induced interleukin-1{beta} processing requires Nod2 and CIAS1/NALP3. J Leukoc Biol 2007, Epub ahead of print.
Agostini L, Martinon F, Burns K, et al.: NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity 2004, 20:319–325.
Stack JH, Beaumont K, Larsen PD, et al.: ICE/caspase-1 inhibitor VX-765 blocks the hypersensitive response to an inflammatory stimulus in monocytes from FCAS patients. J Immunol 2005, 175:2630–2634.
Dowds TA, Masumoto J, Chen FF, et al.: Regulation of cryopyrin/Pypaf1 signaling by pyrin, the familial Mediterranean fever gene product. Biochem Biophys Res Commun 2003, 302:575–580.
Fujisawa A, Kambe N, Saito M, et al.: Disease-associated mutations in CIAS1 induce cathepsin B-dependent rapid cell death of human THP-1 monocytic cells. Blood 2006.
Goldbach-Mansky R, Dailey NJ, Canna SW, et al.: Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med 2006, 355:581–592.
Hawkins PN, Lachmann HJ, McDermott MF: Interleukin-1-receptor antagonist in the Muckle-Wells syndrome. N Engl J Med 2003, 348:2583–2584.
Hoffman HM, Rosengren S, Boyle DL, et al.: Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist. Lancet 2004, 364:1779–1785.
Kastner DL: Familial Mediterranean fever: the genetics of inflammation. Hosp Pract (Off Ed) 1998, 33:131–134, 139–140, 143–136 passim.
Samuels J, Ozen S: Familial Mediterranean fever and the other autoinflammatory syndromes: evaluation of the patient with recurrent fever. Curr Opin Rheumatol 2006, 18:108–117.
Stojanov S, Kastner DL: Familial autoinflammatory diseases: genetics, pathogenesis and treatment. Curr Opin Rheumatol 2005, 17:586–599.
Schaner P, Richards N, Wadhwa A, et al.: Episodic evolution of pyrin in primates: human mutations recapitulate ancestral amino acid states. Nat Genet 2001, 27:318–321.
Chae JJ, Wood G, Masters SL, et al.: The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1beta production. Proc Natl Acad Sci U S A 2006, 103:9982–9987.
Papin S, Cuenin S, Agostini L, et al.: The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing. Cell Death Differ 2007.
Niel E, Scherrmann JM: Colchicine today. Joint Bone Spine 2006, 73:672–678.
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Hoffman, H.M. Hereditary immunologic disorders caused by pyrin and cryopyrin. Curr Allergy Asthma Rep 7, 323–330 (2007). https://doi.org/10.1007/s11882-007-0049-4
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DOI: https://doi.org/10.1007/s11882-007-0049-4