Clinical Reviews in Allergy & Immunology

, Volume 54, Issue 3, pp 454–479 | Cite as

Geoepidemiology and Immunologic Features of Autoinflammatory Diseases: a Comprehensive Review

  • Yvan Jamilloux
  • Alexandre Belot
  • Flora Magnotti
  • Sarah Benezech
  • Mathieu Gerfaud-Valentin
  • Emilie Bourdonnay
  • Thierry Walzer
  • Pascal Sève
  • Thomas Henry


The knowledge on systemic autoinflammatory disorders (SAID) is expanding rapidly and new signalling pathways are being decrypted. The concept of autoinflammation has been proposed since 1999, to define a group of diseases with abnormal innate immunity activation. Since then, more than 30 monogenic SAID have been described. In this review, we first describe inflammasomopathies and SAID related to the interleukin-1 pathway. Recent insights into the pathogenesis of familial Mediterranean fever and the function of Pyrin are detailed. In addition, complex or polygenic SAID, such as Still’s disease or PFAPA syndrome, are also discussed. Then, major players driving autoinflammation, such as type-1 interferonopathies (including the recently described haploinsuffiency in A20 and otulipenia), TNF-associated periodic syndromes, defects in ubiquitination, and SAID with overlapping features of autoimmunity or immunodeficiency. Discoveries of the pathogenic role of mosaicism, intronic defects coupled to the likelihood to identify digenic or polygenic diseases are providing new challenges for physicians and geneticists. This comprehensive review depicts the various SAID, presenting them according to their predominant pathophysiological mechanism, with a particular emphasis on recent findings. Epidemiologic data are also presented. Finally, we propose a practical diagnostic approach to the most common monogenic SAID, based on the most characteristic clinical presentation of these disorders.


Autoinflammatory disorders Inflammasome Pyrin Interleukin-1 Interferonopathies TRAPS 



This work was supported by the Société Nationale Française de Médecine Interne (SNFMI), the Foundation for the Development of Internal Medicine in Europe, and a « poste d’accueil INSERM » (to Y.J.).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    French FMF Consortium (1997) A candidate gene for familial Mediterranean fever. Nat Genet 17:25–31. doi: 10.1038/ng0997-25 CrossRefGoogle Scholar
  2. 2.
    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 90:797–807Google Scholar
  3. 3.
    Xu H, Yang J, Gao W, Li L, Li P, Zhang L et al (2014) Innate immune sensing of bacterial modifications of Rho GTPases by the pyrin inflammasome. Nature 513:237–241. doi: 10.1038/nature13449 PubMedCrossRefGoogle Scholar
  4. 4.
    McDermott MF, Aksentijevich I, Galon J, McDermott EM, Ogunkolade BW, Centola M 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 97:133–144PubMedCrossRefGoogle Scholar
  5. 5.
    Masters SL, Simon A, Aksentijevich I, Kastner DL (2009) Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease (*). Annu rev Immunol 27:621–668. doi: 10.1146/annurev.immunol.25.022106.141627 PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440:237–241. doi: 10.1038/nature04516 PubMedCrossRefGoogle Scholar
  7. 7.
    McGonagle D, McDermott MF (2006) A proposed classification of the immunological diseases. PLoS med 3:e297. doi: 10.1371/journal.pmed.0030297 PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Peckham D, Scambler T, Savic S, McDermott MF (2017) The burgeoning field of innate immune-mediated disease and autoinflammation. J Pathol 241:123–139. doi: 10.1002/path.4812 PubMedCrossRefGoogle Scholar
  9. 9.
    Dinarello CA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519–550. doi: 10.1146/annurev.immunol.021908.132612 PubMedCrossRefGoogle Scholar
  10. 10.
    Martinon F, Burns K, Tschopp J (2002) The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 10:417–426PubMedCrossRefGoogle Scholar
  11. 11.
    Heller H, Sohar E, Pras M (1961) Ethnic distribution and amyloidosis in familial Mediterranean fever (FMF). Pathol Microbiol (Basel) 24:718–723Google Scholar
  12. 12.
    Cakır N, Pamuk ÖN, Derviş E, Imeryüz N, Uslu H, Benian Ö et al (2012) The prevalences of some rheumatic diseases in western Turkey: Havsa study. Rheumatol Int 32:895–908. doi: 10.1007/s00296-010-1699-4 PubMedCrossRefGoogle Scholar
  13. 13.
    Kisacik B, Yildirim B, Tasliyurt T, Ozyurt H, Ozyurt B, Yuce S et al (2009) Increased frequency of familial Mediterranean fever in northern Turkey: a population-based study. Rheumatol Int 29:1307–1309. doi: 10.1007/s00296-009-0849-z PubMedCrossRefGoogle Scholar
  14. 14.
    Sarkisian T, Ajrapetian H, Beglarian A, Shahsuvarian G, Egiazarian A (2008) Familial Mediterranean fever in Armenian population. Georgian Med News 156:105–111Google Scholar
  15. 15.
    Samuels J, Aksentijevich I, Torosyan Y, Centola M, Deng Z, Sood R et al (1998) Familial Mediterranean fever at the millennium. Clinical spectrum, ancient mutations, and a survey of 100 American referrals to the National Institutes of Health. Medicine (Baltimore) 77:268–297CrossRefGoogle Scholar
  16. 16.
    Deltas CC, Mean R, Rossou E, Costi C, Koupepidou P, Hadjiyanni I et al (2002) Familial Mediterranean fever (FMF) mutations occur frequently in the Greek-Cypriot population of Cyprus. Genet Test 6:15–21. doi: 10.1089/109065702760093861 PubMedCrossRefGoogle Scholar
  17. 17.
    La Regina M, Nucera G, Diaco M, Procopio A, Gasbarrini G, Notarnicola C et al (2003) Familial Mediterranean fever is no longer a rare disease in Italy. Eur J hum Genet EJHG 11:50–56. doi: 10.1038/sj.ejhg.5200916 PubMedCrossRefGoogle Scholar
  18. 18.
    Toplak N, Dolezalovà P, Constantin T, Sedivà A, Pašić S, Cižnar P et al (2010) Periodic fever syndromes in eastern and central European countries: results of a pediatric multinational survey. Pediatr Rheumatol Online J 8:29. doi: 10.1186/1546-0096-8-29 PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Migita K, Izumi Y, Jiuchi Y, Iwanaga N, Kawahara C, Agematsu K et al (2016) Familial Mediterranean fever is no longer a rare disease in Japan. Arthritis res Ther 18:175. doi: 10.1186/s13075-016-1071-5 PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Sohar E, Gafni J, Pras M, Heller H (1967) Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J med 43:227–253PubMedCrossRefGoogle Scholar
  21. 21.
    Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T et al (1997) Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 40:1879–1885. doi: 10.1002/1529-0131(199710)40:10<1879::AID-ART23>3.0.CO;2-M PubMedCrossRefGoogle Scholar
  22. 22.
    Berkun Y, Eisenstein EM (2014) Diagnostic criteria of familial Mediterranean fever. Autoimmun Rev 13:388–390. doi: 10.1016/j.autrev.2014.01.045 PubMedCrossRefGoogle Scholar
  23. 23.
    Federici S, Sormani MP, Ozen S, Lachmann HJ, Amaryan G, Woo P et al (2015) Evidence-based provisional clinical classification criteria for autoinflammatory periodic fevers. Ann Rheum Dis 74:799–805. doi: 10.1136/annrheumdis-2014-206580 PubMedCrossRefGoogle Scholar
  24. 24.
    Chae JJ, Cho Y-H, Lee G-S, Cheng J, Liu PP, Feigenbaum L et al (2011) Gain-of-function pyrin mutations induce NLRP3 protein-independent interleukin-1β activation and severe autoinflammation in mice. Immunity 34:755–768. doi: 10.1016/j.immuni.2011.02.020 PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Booty MG, Chae JJ, Masters SL, Remmers EF, Barham B, Le JM et al (2009) Familial Mediterranean fever with a single MEFV mutation: where is the second hit? Arthritis Rheum 60:1851–1861. doi: 10.1002/art.24569 PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Touitou I (2001) The spectrum of familial Mediterranean fever (FMF) mutations. Eur J hum Genet EJHG 9:473–483. doi: 10.1038/sj.ejhg.5200658 PubMedCrossRefGoogle Scholar
  27. 27.
    Tchernitchko DO, Gérard-Blanluet M, Legendre M, Cazeneuve C, Grateau G, Amselem S (2006) Intrafamilial segregation analysis of the p.E148Q MEFV allele in familial Mediterranean fever. Ann Rheum Dis 65:1154–1157. doi: 10.1136/ard.2005.048124 PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Chae JJ, Komarow HD, Cheng J, Wood G, Raben N, Liu PP et al (2003) Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosis. Mol Cell 11:591–604PubMedCrossRefGoogle Scholar
  29. 29.
    Federici S, Calcagno G, Finetti M, Gallizzi R, Meini A, Vitale A et al (2012) Clinical impact of MEFV mutations in children with periodic fever in a prevalent western European Caucasian population. Ann Rheum dis 71:1961–1965. doi: 10.1136/annrheumdis-2011-200977 PubMedCrossRefGoogle Scholar
  30. 30.
    Omenetti A, Carta S, Delfino L, Martini A, Gattorno M, Rubartelli A (2014) Increased NLRP3-dependent interleukin 1β secretion in patients with familial Mediterranean fever: correlation with MEFV genotype. Ann Rheum Dis 73:462–469. doi: 10.1136/annrheumdis-2012-202774 PubMedCrossRefGoogle Scholar
  31. 31.
    Park YH, Wood G, Kastner DL, Chae JJ (2016) Pyrin inflammasome activation and RhoA signaling in the autoinflammatory diseases FMF and HIDS. Nat Immunol 17:914–921. doi: 10.1038/ni.3457 PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Chae JJ, Wood G, Masters SL, Richard K, Park G, Smith BJ et al (2006) 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 103:9982–9987. doi: 10.1073/pnas.0602081103 PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Masters SL, Lagou V, Jéru I, Baker PJ, Van Eyck L, Parry DA et al (2016) Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation. Sci Transl med 8:332ra45. doi: 10.1126/scitranslmed.aaf1471 PubMedCrossRefGoogle Scholar
  34. 34.
    Van Gorp H, Saavedra PHV, de Vasconcelos NM, Van Opdenbosch N, Vande Walle L, Matusiak M et al (2016) Familial Mediterranean fever mutations lift the obligatory requirement for microtubules in pyrin inflammasome activation. Proc Natl Acad Sci U S A 113:14384–14389. doi: 10.1073/pnas.1613156113 PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Kim ML, Chae JJ, Park YH, De Nardo D, Stirzaker RA, Ko H-J et al (2015) Aberrant actin depolymerization triggers the pyrin inflammasome and autoinflammatory disease that is dependent on IL-18, not IL-1β. J Exp Med 212:927–938. doi: 10.1084/jem.20142384 PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Gao W, Yang J, Liu W, Wang Y, Shao F (2016) Site-specific phosphorylation and microtubule dynamics control pyrin inflammasome activation. Proc Natl Acad Sci U S a 113:E4857–E4866. doi: 10.1073/pnas.1601700113 PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Chung LK, Park YH, Zheng Y, Brodsky IE, Hearing P, Kastner DL et al (2016) The Yersinia virulence factor YopM hijacks host kinases to inhibit type III effector-triggered activation of the pyrin inflammasome. Cell Host Microbe 20:296–306. doi: 10.1016/j.chom.2016.07.018 PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Ratner D, Orning MPA, Proulx MK, Wang D, Gavrilin MA, Wewers MD et al (2016) The Yersinia pestis effector YopM inhibits pyrin inflammasome activation. PLoS Pathog 12:e1006035. doi: 10.1371/journal.ppat.1006035 PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Schaner P, Richards N, Wadhwa A, Aksentijevich I, Kastner D, Tucker P et al (2001) Episodic evolution of pyrin in primates: human mutations recapitulate ancestral amino acid states. Nat Genet 27:318–321. doi: 10.1038/85893 PubMedCrossRefGoogle Scholar
  40. 40.
    Houten SM, Kuis W, Duran M, de Koning TJ, van Royen-Kerkhof A, Romeijn GJ et al (1999) Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome. Nat Genet 22:175–177. doi: 10.1038/9691 PubMedCrossRefGoogle Scholar
  41. 41.
    Gershoni-Baruch R, Brik R, Zacks N, Shinawi M, Lidar M, Livneh A (2003) The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial Mediterranean fever. Arthritis Rheum 48:1149–1155. doi: 10.1002/art.10944 PubMedCrossRefGoogle Scholar
  42. 42.
    Vuch J, Marcuzzi A, Bianco AM, Tommasini A, Zanin V, Crovella S (2013) Evolutionary hypothesis of the mevalonate kinase deficiency. Med Hypotheses 80:67–69. doi: 10.1016/j.mehy.2012.10.016 PubMedCrossRefGoogle Scholar
  43. 43.
    van der Hilst JCH, Bodar EJ, Barron KS, Frenkel J, Drenth JPH, van der Meer JWM et al (2008) Long-term follow-up, clinical features, and quality of life in a series of 103 patients with hyperimmunoglobulinemia D syndrome. Medicine (Baltimore) 87:301–310. doi: 10.1097/MD.0b013e318190cfb7 CrossRefGoogle Scholar
  44. 44.
    Zhang S (2016) Natural history of mevalonate kinase deficiency: a literature review. Pediatr Rheumatol Online J 14:30. doi: 10.1186/s12969-016-0091-7 PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Lainka E, Neudorf U, Lohse P, Timmann C, Bielak M, Stojanov S et al (2012) Incidence and clinical features of hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) and spectrum of mevalonate kinase (MVK) mutations in German children. Rheumatol Int 32:3253–3260. doi: 10.1007/s00296-011-2180-8 PubMedCrossRefGoogle Scholar
  46. 46.
    Prieur AM, Griscelli C (1983) Nosologic aspects of systemic forms of very early onset juvenile arthritis. Apropos of 17 cases. Ann Pediatr (Paris) 30:565–569Google Scholar
  47. 47.
    Galeotti C, Georgin-Lavialle S, Sarrabay G, Touitou I, Koné-Paut I (2016) Mevalonate kinase deficiency in 2016. Rev Med Interne. doi: 10.1016/j.revmed.2016.08.019
  48. 48.
    Lindor NM, Arsenault TM, Solomon H, Seidman CE, McEvoy MT (1997) A new autosomal dominant disorder of pyogenic sterile arthritis, pyoderma gangrenosum, and acne: PAPA syndrome. Mayo Clin Proc 72:611–615. doi: 10.1016/S0025-6196(11)63565-9 PubMedCrossRefGoogle Scholar
  49. 49.
    Yang H, Reinherz EL (2006) CD2BP1 modulates CD2-dependent T cell activation via linkage to protein tyrosine phosphatase (PTP)-PEST. J Immunol Baltim md 1950 176:5898–5907Google Scholar
  50. 50.
    Braun-Falco M, Kovnerystyy O, Lohse P, Ruzicka T (2012) Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH)--a new autoinflammatory syndrome distinct from PAPA syndrome. J Am Acad Dermatol 66:409–415. doi: 10.1016/j.jaad.2010.12.025 PubMedCrossRefGoogle Scholar
  51. 51.
    Shoham NG, Centola M, Mansfield E, Hull KM, Wood G, Wise CA et al (2003) Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway. Proc Natl Acad Sci U S a 100:13501–13506. doi: 10.1073/pnas.2135380100 PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Yu J-W, Fernandes-Alnemri T, Datta P, Wu J, Juliana C, Solorzano L et al (2007) Pyrin activates the ASC pyroptosome in response to engagement by autoinflammatory PSTPIP1 mutants. Mol Cell 28:214–227. doi: 10.1016/j.molcel.2007.08.029 PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Holzinger D, Roth J (2016) Alarming consequences - autoinflammatory disease spectrum due to mutations in proline-serine-threonine phosphatase-interacting protein 1. Curr Opin Rheumatol 28:550–559. doi: 10.1097/BOR.0000000000000314 PubMedCrossRefGoogle Scholar
  54. 54.
    Holzinger D, Fassl SK, de Jager W, Lohse P, Röhrig UF, Gattorno M et al (2015) Single amino acid charge switch defines clinically distinct proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1)-associated inflammatory diseases. J Allergy Clin Immunol 136:1337–1345. doi: 10.1016/j.jaci.2015.04.016 PubMedCrossRefGoogle Scholar
  55. 55.
    Leuenberger M, Berner J, Di Lucca J, Fischer L, Kaparos N, Conrad C et al (2016) PASS syndrome: an IL-1-driven autoinflammatory disease. Dermatol Basel Switz 232:254–258. doi: 10.1159/000443648 CrossRefGoogle Scholar
  56. 56.
    Standing ASI, Malinova D, Hong Y, Record J, Moulding D, Blundell MP et al (2017) Autoinflammatory periodic fever, immunodeficiency, and thrombocytopenia (PFIT) caused by mutation in actin-regulatory gene WDR1. J Exp med 214:59–71. doi: 10.1084/jem.20161228 PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Matzinger P (2002) The danger model: a renewed sense of self. Science 296:301–305. doi: 10.1126/science.1071059 PubMedCrossRefGoogle Scholar
  58. 58.
    Bergsbaken T, Fink SL, Cookson BT (2009) Pyroptosis: host cell death and inflammation. Nat rev Microbiol 7:99–109. doi: 10.1038/nrmicro2070 PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Jamilloux Y, Henry T (2013) The inflammasomes: platforms of innate immunity. Médecine Sci MS 29:975–984. doi: 10.1051/medsci/20132911013 PubMedCrossRefGoogle Scholar
  60. 60.
    Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD (2001) Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet 29:301–305. doi: 10.1038/ng756 PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Mehr S, Allen R, Boros C, Adib N, Kakakios A, Turner PJ et al (2016) Cryopyrin-associated periodic syndrome in Australian children and adults: epidemiological, clinical and treatment characteristics. J Paediatr Child Health 52:889–895. doi: 10.1111/jpc.13270 PubMedCrossRefGoogle Scholar
  62. 62.
    Cuisset L, Jeru I, Dumont B, Fabre A, Cochet E, Le Bozec J et al (2011) Mutations in the autoinflammatory cryopyrin-associated periodic syndrome gene: epidemiological study and lessons from eight years of genetic analysis in France. Ann Rheum Dis 70:495–499. doi: 10.1136/ard.2010.138420 PubMedCrossRefGoogle Scholar
  63. 63.
    Lainka E, Neudorf U, Lohse P, Timmann C, Bielak M, Stojanov S et al (2010) Analysis of cryopyrin-associated periodic syndromes (CAPS) in German children: epidemiological, clinical and genetic characteristics. Klin Padiatr 222:356–361. doi: 10.1055/s-0030-1265181 PubMedCrossRefGoogle Scholar
  64. 64.
    Tanaka N, Izawa K, Saito MK, Sakuma M, Oshima K, Ohara O et al (2011) High incidence of NLRP3 somatic mosaicism in patients with chronic infantile neurologic, cutaneous, articular syndrome: results of an International Multicenter Collaborative Study. Arthritis Rheum 63:3625–3632. doi: 10.1002/art.30512 PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Levy R, Gérard L, Kuemmerle-Deschner J, Lachmann HJ, Koné-Paut I, Cantarini L et al (2015) Phenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome: a series of 136 patients from the Eurofever registry. Ann Rheum Dis 74:2043–2049. doi: 10.1136/annrheumdis-2013-204991 PubMedCrossRefGoogle Scholar
  66. 66.
    Rowczenio DM, Trojer H, Russell T, Baginska A, Lane T, Stewart NM et al (2013) Clinical characteristics in subjects with NLRP3 V198M diagnosed at a single UK center and a review of the literature. Arthritis res Ther 15:R30. doi: 10.1186/ar4171 PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Goldbach-Mansky R, Dailey NJ, Canna SW, Gelabert A, Jones J, Rubin BI et al (2006) Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med 355:581–592. doi: 10.1056/NEJMoa055137 PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Goldbach-Mansky R (2009) Blocking interleukin-1 in rheumatic diseases. Ann N Y Acad Sci 1182:111–123. doi: 10.1111/j.1749-6632.2009.05159.x PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Tschopp J, Schroder K (2010) NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production? Nat Rev Immunol 10:210–215. doi: 10.1038/nri2725 PubMedCrossRefGoogle Scholar
  70. 70.
    Martinon F, Mayor A, Tschopp J (2009) The inflammasomes: guardians of the body. Annu rev Immunol 27:229–265. doi: 10.1146/annurev.immunol.021908.132715 PubMedCrossRefGoogle Scholar
  71. 71.
    Pétrilli V, Papin S, Dostert C, Mayor A, Martinon F, Tschopp J (2007) Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ 14:1583–1589. doi: 10.1038/sj.cdd.4402195 PubMedCrossRefGoogle Scholar
  72. 72.
    Baroja-Mazo A, Martín-Sánchez F, Gomez AI, Martínez CM, Amores-Iniesta J, Compan V et al (2014) The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response. Nat Immunol 15:738–748. doi: 10.1038/ni.2919 PubMedCrossRefGoogle Scholar
  73. 73.
    Hoffman HM, Broderick L (2017) Editorial: it just takes one: somatic mosaicism in autoinflammatory disease. Arthritis Rheumatol Hoboken NJ 69:253–256. doi: 10.1002/art.39961 CrossRefGoogle Scholar
  74. 74.
    Nakagawa K, Gonzalez-Roca E, Souto A, Kawai T, Umebayashi H, Campistol JM et al (2015) Somatic NLRP3 mosaicism in Muckle-Wells syndrome. A genetic mechanism shared by different phenotypes of cryopyrin-associated periodic syndromes. Ann Rheum Dis 74:603–610. doi: 10.1136/annrheumdis-2013-204361 PubMedCrossRefGoogle Scholar
  75. 75.
    Canna SW, de Jesus AA, Gouni S, Brooks SR, Marrero B, Liu Y et al (2014) An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat Genet 46:1140–1146. doi: 10.1038/ng.3089 PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Romberg N, Al Moussawi K, Nelson-Williams C, Stiegler AL, Loring E, Choi M et al (2014) Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation. Nat Genet 46:1135–1139. doi: 10.1038/ng.3066 PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Volker-Touw CML, de Koning HD, Giltay JC, de Kovel CGF, van Kempen TS, Oberndorff KMEJ et al (2017) Erythematous nodes, urticarial rash and arthralgias in a large pedigree with NLRC4-related autoinflammatory disease, expansion of the phenotype. Br J Dermatol 176:244–248. doi: 10.1111/bjd.14757 PubMedCrossRefGoogle Scholar
  78. 78.
    Kitamura A, Sasaki Y, Abe T, Kano H, Yasutomo K (2014) An inherited mutation in NLRC4 causes autoinflammation in human and mice. J Exp Med 211:2385–2396. doi: 10.1084/jem.20141091 PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Kawasaki Y, Oda H, Ito J, Niwa A, Tanaka T, Hijikata A et al (2017) Identification of a high-frequency somatic NLRC4 mutation as a cause of autoinflammation by pluripotent cell-based phenotype dissection. Arthritis Rheumatol Hoboken NJ 69:447–459. doi: 10.1002/art.39960 CrossRefGoogle Scholar
  80. 80.
    Canna SW, Girard C, Malle L, de Jesus A, Romberg N, Kelsen J et al (2016) Life-threatening NLRC4-associated hyperinflammation successfully treated with IL-18 inhibition. J Allergy Clin Immunol. doi: 10.1016/j.jaci.2016.10.022
  81. 81.
    Coers J, Vance RE, Fontana MF, Dietrich WF (2007) Restriction of Legionella pneumophila growth in macrophages requires the concerted action of cytokine and Naip5/Ipaf signalling pathways. Cell Microbiol 9:2344–2357. doi: 10.1111/j.1462-5822.2007.00963.x PubMedCrossRefGoogle Scholar
  82. 82.
    Yang J, Zhao Y, Shi J, Shao F (2013) Human NAIP and mouse NAIP1 recognize bacterial type III secretion needle protein for inflammasome activation. Proc Natl Acad Sci U S A 110:14408–14413. doi: 10.1073/pnas.1306376110 PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Kortmann J, Brubaker SW, Monack DM (2015) Cutting edge: inflammasome activation in primary human macrophages is dependent on flagellin. J Immunol Baltim md 1950 195:815–819. doi: 10.4049/jimmunol.1403100 CrossRefGoogle Scholar
  84. 84.
    Raghawan AK, Sripada A, Gopinath G, Pushpanjali P, Kumar Y, Radha V et al (2017) A disease-associated mutant of NLRC4 shows enhanced interaction with SUG1 leading to constitutive FADD-dependent caspase-8 activation and cell death. J Biol Chem 292:1218–1230. doi: 10.1074/jbc.M116.763979 PubMedCrossRefGoogle Scholar
  85. 85.
    Zhong FL, Mamaï O, Sborgi L, Boussofara L, Hopkins R, Robinson K et al (2016) Germline NLRP1 mutations cause skin inflammatory and cancer susceptibility syndromes via inflammasome activation. Cell 167:187–202.e17. doi: 10.1016/j.cell.2016.09.001 PubMedCrossRefGoogle Scholar
  86. 86.
    Soler VJ, Tran-Viet K-N, Galiacy SD, Limviphuvadh V, Klemm TP, St Germain E et al (2013) Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis. J Med Genet 50:246–254. doi: 10.1136/jmedgenet-2012-101325 PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Grandemange S, Sanchez E, Louis-Plence P, Tran Mau-Them F, Bessis D, Coubes C et al (2016) A new autoinflammatory and autoimmune syndrome associated with NLRP1 mutations: NAIAD (NLRP1-associated autoinflammation with arthritis and dyskeratosis). Ann Rheum Dis. doi: 10.1136/annrheumdis-2016-210021
  88. 88.
    Masters SL, Gerlic M, Metcalf D, Preston S, Pellegrini M, O’Donnell JA et al (2012) NLRP1 inflammasome activation induces pyroptosis of hematopoietic progenitor cells. Immunity 37:1009–1023. doi: 10.1016/j.immuni.2012.08.027 PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Jéru I, Duquesnoy P, Fernandes-Alnemri T, Cochet E, Yu JW, Lackmy-Port-Lis M et al (2008) Mutations in NALP12 cause hereditary periodic fever syndromes. Proc Natl Acad Sci U S A 105:1614–1619. doi: 10.1073/pnas.0708616105 PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Borghini S, Tassi S, Chiesa S, Caroli F, Carta S, Caorsi R et al (2011) Clinical presentation and pathogenesis of cold-induced autoinflammatory disease in a family with recurrence of an NLRP12 mutation. Arthritis Rheum 63:830–839. doi: 10.1002/art.30170 PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Jéru I, Le Borgne G, Cochet E, Hayrapetyan H, Duquesnoy P, Grateau G et al (2011) Identification and functional consequences of a recurrent NLRP12 missense mutation in periodic fever syndromes. Arthritis Rheum 63:1459–1464. doi: 10.1002/art.30241 PubMedCrossRefGoogle Scholar
  92. 92.
    Vladimer GI, Weng D, Paquette SWM, Vanaja SK, Rathinam VAK, Aune MH et al (2012) The NLRP12 inflammasome recognizes Yersinia pestis. Immunity 37:96–107. doi: 10.1016/j.immuni.2012.07.006 PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Miceli-Richard C, Lesage S, Rybojad M, Prieur AM, Manouvrier-Hanu S, Häfner R et al (2001) CARD15 mutations in Blau syndrome. Nat Genet 29:19–20. doi: 10.1038/ng720 PubMedCrossRefGoogle Scholar
  94. 94.
    Rosé CD, Pans S, Casteels I, Anton J, Bader-Meunier B, Brissaud P et al (2015) Blau syndrome: cross-sectional data from a multicentre study of clinical, radiological and functional outcomes. Rheumatol Oxf Engl 54:1008–1016. doi: 10.1093/rheumatology/keu437 CrossRefGoogle Scholar
  95. 95.
    Caso F, Costa L, Rigante D, Vitale A, Cimaz R, Lucherini OM et al (2014) Caveats and truths in genetic, clinical, autoimmune and autoinflammatory issues in Blau syndrome and early onset sarcoidosis. Autoimmun Rev 13:1220–1229. doi: 10.1016/j.autrev.2014.08.010 PubMedCrossRefGoogle Scholar
  96. 96.
    Kanazawa N, Okafuji I, Kambe N, Nishikomori R, Nakata-Hizume M, Nagai S et al (2005) Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: common genetic etiology with Blau syndrome. Blood 105:1195–1197. doi: 10.1182/blood-2004-07-2972 PubMedCrossRefGoogle Scholar
  97. 97.
    Kobayashi K, Inohara N, Hernandez LD, Galán JE, Núñez G, Janeway CA et al (2002) RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature 416:194–199. doi: 10.1038/416194a PubMedCrossRefGoogle Scholar
  98. 98.
    Magalhaes JG, Lee J, Geddes K, Rubino S, Philpott DJ, Girardin SE (2011) Essential role of Rip2 in the modulation of innate and adaptive immunity triggered by Nod1 and Nod2 ligands. Eur J Immunol 41:1445–1455. doi: 10.1002/eji.201040827 PubMedCrossRefGoogle Scholar
  99. 99.
    Aróstegui JI, Arnal C, Merino R, Modesto C, Antonia Carballo M, Moreno P et al (2007) NOD2 gene-associated pediatric granulomatous arthritis: clinical diversity, novel and recurrent mutations, and evidence of clinical improvement with interleukin-1 blockade in a Spanish cohort. Arthritis Rheum 56:3805–3813. doi: 10.1002/art.22966 PubMedCrossRefGoogle Scholar
  100. 100.
    Majeed HA, Kalaawi M, Mohanty D, Teebi AS, Tunjekar MF, al-Gharbawy F et al (1989) Congenital dyserythropoietic anemia and chronic recurrent multifocal osteomyelitis in three related children and the association with sweet syndrome in two siblings. J Pediatr 115:730–734PubMedCrossRefGoogle Scholar
  101. 101.
    Ferguson PJ, Chen S, Tayeh MK, Ochoa L, Leal SM, Pelet A et al (2005) Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome). J Med Genet 42:551–557. doi: 10.1136/jmg.2005.030759 PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Valdearcos M, Esquinas E, Meana C, Peña L, Gil-de-Gómez L, Balsinde J et al (2012) Lipin-2 reduces proinflammatory signaling induced by saturated fatty acids in macrophages. J Biol Chem 287:10894–10904. doi: 10.1074/jbc.M112.342915 PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Herlin T, Fiirgaard B, Bjerre M, Kerndrup G, Hasle H, Bing X et al (2013) Efficacy of anti-IL-1 treatment in Majeed syndrome. Ann Rheum Dis 72:410–413. doi: 10.1136/annrheumdis-2012-201818 PubMedCrossRefGoogle Scholar
  104. 104.
    Aksentijevich I, Masters SL, Ferguson PJ, Dancey P, Frenkel J, van Royen-Kerkhoff A et al (2009) An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J med 360:2426–2437. doi: 10.1056/NEJMoa0807865 PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Reddy S, Jia S, Geoffrey R, Lorier R, Suchi M, Broeckel U et al (2009) An autoinflammatory disease due to homozygous deletion of the IL1RN locus. N Engl J Med 360:2438–2444. doi: 10.1056/NEJMoa0809568 PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Jesus AA, Osman M, Silva CA, Kim PW, Pham T-H, Gadina M et al (2011) A novel mutation of IL1RN in the deficiency of interleukin-1 receptor antagonist syndrome: description of two unrelated cases from Brazil. Arthritis Rheum 63:4007–4017. doi: 10.1002/art.30588 PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Marrakchi S, Guigue P, Renshaw BR, Puel A, Pei X-Y, Fraitag S et al (2011) Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med 365:620–628. doi: 10.1056/NEJMoa1013068 PubMedCrossRefGoogle Scholar
  108. 108.
    Sugiura T, Kawaguchi Y, Harigai M, Terajima-Ichida H, Kitamura Y, Furuya T et al (2002) Association between adult-onset Still’s disease and interleukin-18 gene polymorphisms. Genes Immun 3:394–399. doi: 10.1038/sj.gene.6363922 PubMedCrossRefGoogle Scholar
  109. 109.
    Kanazawa N, Nakamura T, Mikita N, Furukawa F (2013) Novel IL36RN mutation in a Japanese case of early onset generalized pustular psoriasis. J Dermatol 40:749–751. doi: 10.1111/1346-8138.12227 PubMedCrossRefGoogle Scholar
  110. 110.
    Blumberg H, Dinh H, Trueblood ES, Pretorius J, Kugler D, Weng N et al (2007) Opposing activities of two novel members of the IL-1 ligand family regulate skin inflammation. J Exp Med 204:2603–2614. doi: 10.1084/jem.20070157 PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Martini A (2012) Systemic juvenile idiopathic arthritis. Autoimmun Rev 12:56–59. doi: 10.1016/j.autrev.2012.07.022 PubMedCrossRefGoogle Scholar
  112. 112.
    Behrens EM, Beukelman T, Gallo L, Spangler J, Rosenkranz M, Arkachaisri T et al (2008) Evaluation of the presentation of systemic onset juvenile rheumatoid arthritis: data from the Pennsylvania Systemic Onset Juvenile Arthritis Registry (PASOJAR). J Rheumatol 35:343–348PubMedGoogle Scholar
  113. 113.
    Feldman BM, Birdi N, Boone JE, Dent PB, Duffy CM, Ellsworth JE et al (1996) Seasonal onset of systemic-onset juvenile rheumatoid arthritis. J Pediatr 129:513–518PubMedCrossRefGoogle Scholar
  114. 114.
    Modesto C, Antón J, Rodriguez B, Bou R, Arnal C, Ros J et al (2010) Incidence and prevalence of juvenile idiopathic arthritis in Catalonia (Spain). Scand J Rheumatol 39:472–479. doi: 10.3109/03009741003742722 PubMedCrossRefGoogle Scholar
  115. 115.
    Schneider R, Laxer RM (1998) Systemic onset juvenile rheumatoid arthritis. Baillieres Clin Rheumatol 12:245–271PubMedCrossRefGoogle Scholar
  116. 116.
    Pruunsild C, Uibo K, Liivamägi H, Tarraste S, Talvik T, Pelkonen P (2007) Incidence of juvenile idiopathic arthritis in children in Estonia: a prospective population-based study. Scand J Rheumatol 36:7–13. doi: 10.1080/03009740601089259 PubMedCrossRefGoogle Scholar
  117. 117.
    Huemer C, Huemer M, Dorner T, Falger J, Schacherl H, Bernecker M et al (2001) Incidence of pediatric rheumatic diseases in a regional population in Austria. J Rheumatol 28:2116–2119PubMedGoogle Scholar
  118. 118.
    Kaipiainen-Seppänen O, Savolainen A (2001) Changes in the incidence of juvenile rheumatoid arthritis in Finland. Rheumatol Oxf Engl 40:928–932CrossRefGoogle Scholar
  119. 119.
    Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J (2005) Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med 201:1479–1486. doi: 10.1084/jem.20050473 PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Jamilloux Y, Gerfaud-Valentin M, Martinon F, Belot A, Henry T, Sève P (2015) Pathogenesis of adult-onset Still’s disease: new insights from the juvenile counterpart. Immunol Res 61:53–62. doi: 10.1007/s12026-014-8561-9 PubMedCrossRefGoogle Scholar
  121. 121.
    Ombrello MJ, Remmers EF, Tachmazidou I, Grom A, Foell D, Haas J-P et al (2015) HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis. Proc Natl Acad Sci U S A 112:15970–15975. doi: 10.1073/pnas.1520779112 PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Ombrello MJ, Arthur VL, Remmers EF, Hinks A, Tachmazidou I, Grom AA et al (2016) Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications. Ann Rheum dis. doi: 10.1136/annrheumdis-2016-210324
  123. 123.
    Wakil SM, Monies DM, Abouelhoda M, Al-Tassan N, Al-Dusery H, Naim EA et al (2015) Association of a mutation in LACC1 with a monogenic form of systemic juvenile idiopathic arthritis. Arthritis Rheumatol Hoboken NJ 67:288–295. doi: 10.1002/art.38877 CrossRefGoogle Scholar
  124. 124.
    Cader MZ, Boroviak K, Zhang Q, Assadi G, Kempster SL, Sewell GW et al (2016) C13orf31 (FAMIN) is a central regulator of immunometabolic function. Nat Immunol 17:1046–1056. doi: 10.1038/ni.3532 PubMedCrossRefGoogle Scholar
  125. 125.
    Gerfaud-Valentin M, Jamilloux Y, Iwaz J, Sève P (2014) Adult-onset Still’s disease. Autoimmun Rev 13:708–722. doi: 10.1016/j.autrev.2014.01.058 PubMedCrossRefGoogle Scholar
  126. 126.
    Gerfaud-Valentin M, Maucort-Boulch D, Hot A, Iwaz J, Ninet J, Durieu I et al (2014) Adult-onset still disease: manifestations, treatment, outcome, and prognostic factors in 57 patients. Medicine (Baltimore) 93:91–99. doi: 10.1097/MD.0000000000000021 CrossRefGoogle Scholar
  127. 127.
    Pouchot J, Sampalis JS, Beaudet F, Carette S, Decary F, Salusinsky-Sternbach M et al (1991) Adult Still’s disease: manifestations, disease course, and outcome in 62 patients. Medicine (Baltimore) 70:118–136CrossRefGoogle Scholar
  128. 128.
    Ichiki H, Shishido M, Nishiyama S (1992) Two cases of adult onset of Still’s disease in the elderly. Nihon Ronen Igakkai Zasshi Jpn J Geriatr 29:960–964CrossRefGoogle Scholar
  129. 129.
    Magadur-Joly G, Billaud E, Barrier JH, Pennec YL, Masson C, Renou P et al (1995) Epidemiology of adult Still’s disease: estimate of the incidence by a retrospective study in west France. Ann Rheum dis 54:587–590PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Wakai K, Ohta A, Tamakoshi A, Ohno Y, Kawamura T, Aoki R et al (1997) Estimated prevalence and incidence of adult Still’s disease: findings by a nationwide epidemiological survey in Japan. J Epidemiol 7:221–225PubMedCrossRefGoogle Scholar
  131. 131.
    Evensen KJ, Nossent HC (2006) Epidemiology and outcome of adult-onset Still’s disease in northern Norway. Scand J Rheumatol 35:48–51. doi: 10.1080/03009740510026616 PubMedCrossRefGoogle Scholar
  132. 132.
    Chen D-Y, Lan J-L, Lin F-J, Hsieh T-Y (2005) Association of intercellular adhesion molecule-1 with clinical manifestations and interleukin-18 in patients with active, untreated adult-onset Still’s disease. Arthritis Rheum 53:320–327. doi: 10.1002/art.21164 PubMedCrossRefGoogle Scholar
  133. 133.
    Narula N, Narula T, Abril A (2015) Seizing the clinical presentation in adult onset Still’s disease. An extensive literature review. Autoimmun rev 14:472–477. doi: 10.1016/j.autrev.2015.01.007 PubMedCrossRefGoogle Scholar
  134. 134.
    Liozon E, Ly KH, Vidal-Cathala E, Fauchais A-L (2014) Adult-onset Still’s disease as a manifestation of malignancy: report of a patient with melanoma and literature review. Rev Médecine Interne Fondée par Société Natl Francaise Médecine Interne 35:60–64. doi: 10.1016/j.revmed.2013.02.014 CrossRefGoogle Scholar
  135. 135.
    Jamilloux Y, Gerfaud-Valentin M, Henry T, Sève P (2015) Treatment of adult-onset Still’s disease: a review. Ther Clin Risk Manag 11:33–43. doi: 10.2147/TCRM.S64951 PubMedCrossRefGoogle Scholar
  136. 136.
    Marshall GS, Edwards KM, Butler J, Lawton AR (1987) Syndrome of periodic fever, pharyngitis, and aphthous stomatitis. J Pediatr 110:43–46PubMedCrossRefGoogle Scholar
  137. 137.
    Vigo G, Zulian F (2012) Periodic fevers with aphthous stomatitis, pharyngitis, and adenitis (PFAPA). Autoimmun Rev 12:52–55. doi: 10.1016/j.autrev.2012.07.021 PubMedCrossRefGoogle Scholar
  138. 138.
    Rigante D, Vitale A, Natale MF, Lopalco G, Andreozzi L, Frediani B et al (2017) A comprehensive comparison between pediatric and adult patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenopathy (PFAPA) syndrome. Clin Rheumatol 36:463–468. doi: 10.1007/s10067-016-3317-7 PubMedCrossRefGoogle Scholar
  139. 139.
    Feder HM, Salazar JC (2010) A clinical review of 105 patients with PFAPA (a periodic fever syndrome). Acta Paediatr Oslo nor 1992 99:178–184. doi: 10.1111/j.1651-2227.2009.01554.x CrossRefGoogle Scholar
  140. 140.
    Førsvoll J, Kristoffersen EK, Øymar K (2013) Incidence, clinical characteristics and outcome in Norwegian children with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome; a population-based study. Acta Paediatr Oslo nor 1992 102:187–192. doi: 10.1111/apa.12069 CrossRefGoogle Scholar
  141. 141.
    Hofer M, Pillet P, Cochard M-M, Berg S, Krol P, Kone-Paut I et al (2014) International periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome cohort: description of distinct phenotypes in 301 patients. Rheumatol Oxf Engl 53:1125–1129. doi: 10.1093/rheumatology/ket460 CrossRefGoogle Scholar
  142. 142.
    Theodoropoulou K, Vanoni F, Hofer M (2016) Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome: a review of the pathogenesis. Curr Rheumatol Rep 18:18. doi: 10.1007/s11926-016-0567-y PubMedCrossRefGoogle Scholar
  143. 143.
    Cheung MS, Theodoropoulou K, Lugrin J, Martinon F, Busso N, Hofer M (2017) Periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome is associated with a CARD8 variant unable to bind the NLRP3 inflammasome. J Immunol 198:2063–2069. doi: 10.4049/jimmunol.1600760 PubMedCrossRefGoogle Scholar
  144. 144.
    Stojanov S, Lapidus S, Chitkara P, Feder H, Salazar JC, Fleisher TA et al (2011) Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a disorder of innate immunity and Th1 activation responsive to IL-1 blockade. Proc Natl Acad Sci U S A 108:7148–7153. doi: 10.1073/pnas.1103681108 PubMedPubMedCentralCrossRefGoogle Scholar
  145. 145.
    Cochard M, Clet J, Le L, Pillet P, Onrubia X, Guéron T et al (2010) PFAPA syndrome is not a sporadic disease. Rheumatol Oxf Engl 49:1984–1987. doi: 10.1093/rheumatology/keq187 CrossRefGoogle Scholar
  146. 146.
    Perko D, Debeljak M, Toplak N, Avčin T (2015) Clinical features and genetic background of the periodic fever syndrome with aphthous stomatitis, pharyngitis, and adenitis: a single center longitudinal study of 81 patients. Mediat Inflamm 2015:293417. doi: 10.1155/2015/293417 CrossRefGoogle Scholar
  147. 147.
    Ter Haar N, Lachmann H, Özen S, Woo P, Uziel Y, Modesto C et al (2013) Treatment of autoinflammatory diseases: results from the Eurofever registry and a literature review. Ann Rheum Dis 72:678–685. doi: 10.1136/annrheumdis-2011-201268 PubMedCrossRefGoogle Scholar
  148. 148.
    Burton MJ, Pollard AJ, Ramsden JD, Chong LY, Venekamp RP (2014) Tonsillectomy for periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA). Cochrane Database Syst Rev 11:CD008669. doi: 10.1002/14651858.CD008669.pub2 CrossRefGoogle Scholar
  149. 149.
    Vanoni F, Theodoropoulou K, Hofer M (2016) PFAPA syndrome: a review on treatment and outcome. Pediatr Rheumatol Online J 14. doi: 10.1186/s12969-016-0101-9
  150. 150.
    Schnitzler L, Schubert B, Verret JL, Simon L, Alquier P (1976) Cutaneous manifestations in disseminated intravascular coagulation syndrome. Ann Dermatol Syphiligr (Paris) 103:124–134Google Scholar
  151. 151.
    Lipsker D (2010) The Schnitzler syndrome. Orphanet J Rare Dis 5:38. doi: 10.1186/1750-1172-5-38 PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Simon A, Asli B, Braun-Falco M, De Koning H, Fermand J-P, Grattan C et al (2013) Schnitzler’s syndrome: diagnosis, treatment, and follow-up. Allergy 68:562–568. doi: 10.1111/all.12129 PubMedCrossRefGoogle Scholar
  153. 153.
    de Koning HD, Schalkwijk J, van der Meer JWM, Simon A (2011) Successful canakinumab treatment identifies IL-1β as a pivotal mediator in Schnitzler syndrome. J Allergy Clin Immunol 128:1352–1354. doi: 10.1016/j.jaci.2011.05.023 PubMedCrossRefGoogle Scholar
  154. 154.
    de Koning HD, Schalkwijk J, van der Ven-Jongekrijg J, Stoffels M, van der Meer JWM, Simon A (2013) Sustained efficacy of the monoclonal anti-interleukin-1 beta antibody canakinumab in a 9-month trial in Schnitzler’s syndrome. Ann Rheum Dis 72:1634–1638. doi: 10.1136/annrheumdis-2012-202192 PubMedCrossRefGoogle Scholar
  155. 155.
    de Koning HD, van Gijn ME, Stoffels M, Jongekrijg J, Zeeuwen PLJM, Elferink MG et al (2015) Myeloid lineage-restricted somatic mosaicism of NLRP3 mutations in patients with variant Schnitzler syndrome. J Allergy Clin Immunol 135:561–564. doi: 10.1016/j.jaci.2014.07.050 PubMedCrossRefGoogle Scholar
  156. 156.
    Zhou Q, Aksentijevich I, Wood GM, Walts AD, Hoffmann P, Remmers EF et al (2015) Brief report: cryopyrin-associated periodic syndrome caused by a myeloid-restricted somatic NLRP3 mutation. Arthritis Rheumatol Hoboken NJ 67:2482–2486. doi: 10.1002/art.39190 CrossRefGoogle Scholar
  157. 157.
    Crow YJ (2011) Type I interferonopathies: a novel set of inborn errors of immunity. Ann N Y Acad Sci 1238:91–98. doi: 10.1111/j.1749-6632.2011.06220.x PubMedCrossRefGoogle Scholar
  158. 158.
    Rodero MP, Crow YJ (2016) Type I interferon-mediated monogenic autoinflammation: the type I interferonopathies, a conceptual overview. J Exp med 213:2527–2538. doi: 10.1084/jem.20161596 PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Picard C, Mathieu A-L, Hasan U, Henry T, Jamilloux Y, Walzer T et al (2015) Inherited anomalies of innate immune receptors in pediatric-onset inflammatory diseases. Autoimmun Rev 14:1147–1153. doi: 10.1016/j.autrev.2015.08.002 PubMedCrossRefGoogle Scholar
  160. 160.
    Picard C, Belot A (2016) Type I interferonopathies. Literature review. Rev Med Interne. doi: 10.1016/j.revmed.2016.08.016
  161. 161.
    Atianand MK, Fitzgerald KA (2013) Molecular basis of DNA recognition in the immune system. J Immunol Baltim md 1950 190:1911–1918. doi: 10.4049/jimmunol.1203162 CrossRefGoogle Scholar
  162. 162.
    Chen Q, Sun L, Chen ZJ (2016) Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing. Nat Immunol 17:1142–1149. doi: 10.1038/ni.3558 PubMedCrossRefGoogle Scholar
  163. 163.
    Frémond M-L, Rodero MP, Jeremiah N, Belot A, Jeziorski E, Duffy D et al (2016) Efficacy of the Janus kinase 1/2 inhibitor ruxolitinib in the treatment of vasculopathy associated with TMEM173-activating mutations in 3 children. J Allergy Clin Immunol 138:1752–1755. doi: 10.1016/j.jaci.2016.07.015 PubMedCrossRefGoogle Scholar
  164. 164.
    Aicardi J, Goutières F (1984) A progressive familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis. Ann Neurol 15:49–54. doi: 10.1002/ana.410150109 PubMedCrossRefGoogle Scholar
  165. 165.
    Rice GI, del Toro Duany Y, Jenkinson EM, Forte GMA, Anderson BH, Ariaudo G et al (2014) Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling. Nat Genet 46:503–509. doi: 10.1038/ng.2933 PubMedPubMedCentralCrossRefGoogle Scholar
  166. 166.
    Liu Y, Jesus AA, Marrero B, Yang D, Ramsey SE, Montealegre Sanchez GA et al (2014) Activated STING in a vascular and pulmonary syndrome. N Engl J Med 371:507–518. doi: 10.1056/NEJMoa1312625 PubMedPubMedCentralCrossRefGoogle Scholar
  167. 167.
    Jeremiah N, Neven B, Gentili M, Callebaut I, Maschalidi S, Stolzenberg M-C et al (2014) Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations. J Clin Invest 124:5516–5520. doi: 10.1172/JCI79100 PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Crow YJ, Casanova J-L (2014) STING-associated vasculopathy with onset in infancy—a new interferonopathy. N Engl J Med 371:568–571. doi: 10.1056/NEJMe1407246 PubMedCrossRefGoogle Scholar
  169. 169.
    Agarwal AK, Xing C, DeMartino GN, Mizrachi D, Hernandez MD, Sousa AB 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. doi: 10.1016/j.ajhg.2010.10.031 PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Arima K, Kinoshita A, Mishima H, Kanazawa N, Kaneko T, Mizushima T et al (2011) Proteasome assembly defect due to a proteasome subunit beta type 8 (PSMB8) mutation causes the autoinflammatory disorder, Nakajo-Nishimura syndrome. Proc Natl Acad Sci U S A 108:14914–14919. doi: 10.1073/pnas.1106015108 PubMedPubMedCentralCrossRefGoogle Scholar
  171. 171.
    Kitamura A, Maekawa Y, Uehara H, Izumi K, Kawachi I, Nishizawa M et al (2011) A mutation in the immunoproteasome subunit PSMB8 causes autoinflammation and lipodystrophy in humans. J Clin Invest 121:4150–4160. doi: 10.1172/JCI58414 PubMedPubMedCentralCrossRefGoogle Scholar
  172. 172.
    Brehm A, Liu Y, Sheikh A, Marrero B, Omoyinmi E, Zhou Q 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. doi: 10.1172/JCI81260 PubMedPubMedCentralCrossRefGoogle Scholar
  173. 173.
    Murarasu A, Dodé C, Sarrabay G, Klein I, Papo T, Sacré K (2017) Digenic MEFV/TNFRSF1A autoinflammatory syndrome with relapsing aseptic neutrophilic meningitis and chronic myelitis. Clin Exp RheumatolGoogle Scholar
  174. 174.
    Stoffels M, Kastner DL (2016) Old dogs, new tricks: monogenic autoinflammatory disease unleashed. Annu Rev Genomics Hum Genet 17:245–272. doi: 10.1146/annurev-genom-090413-025334 PubMedCrossRefGoogle Scholar
  175. 175.
    McDermott A, Jacks J, Kessler M, Emanuel PD, Gao L (2015) Proteasome-associated autoinflammatory syndromes: advances in pathogeneses, clinical presentations, diagnosis, and management. Int J Dermatol 54:121–129. doi: 10.1111/ijd.12695 PubMedCrossRefGoogle Scholar
  176. 176.
    Jang M-A, Kim EK, Now H, Nguyen NTH, Kim W-J, Yoo J-Y et al (2015) Mutations in DDX58, which encodes RIG-I, cause atypical Singleton-Merten syndrome. Am J Hum Genet 96:266–274. doi: 10.1016/j.ajhg.2014.11.019 PubMedPubMedCentralCrossRefGoogle Scholar
  177. 177.
    Briggs TA, Rice GI, Daly S, Urquhart J, Gornall H, Bader-Meunier B et al (2011) Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature. Nat Genet 43:127–131. doi: 10.1038/ng.748 PubMedCrossRefGoogle Scholar
  178. 178.
    Lausch E, Janecke A, Bros M, Trojandt S, Alanay Y, De Laet C et al (2011) Genetic deficiency of tartrate-resistant acid phosphatase associated with skeletal dysplasia, cerebral calcifications and autoimmunity. Nat Genet 43:132–137. doi: 10.1038/ng.749 PubMedCrossRefGoogle Scholar
  179. 179.
    Briggs TA, Rice GI, Adib N, Ades L, Barete S, Baskar K et al (2016) Spondyloenchondrodysplasia due to mutations in ACP5: a comprehensive survey. J Clin Immunol 36:220–234. doi: 10.1007/s10875-016-0252-y PubMedPubMedCentralCrossRefGoogle Scholar
  180. 180.
    Starokadomskyy P, Gemelli T, Rios JJ, Xing C, Wang RC, Li H et al (2016) DNA polymerase-α regulates the activation of type I interferons through cytosolic RNA:DNA synthesis. Nat Immunol 17:495–504. doi: 10.1038/ni.3409 PubMedPubMedCentralCrossRefGoogle Scholar
  181. 181.
    Fernandez-Guarino M, Torrelo A, Fernandez-Lorente M, Fraile G, García-Sagredo JM, Jaén P (2008) X-linked reticulate pigmentary disorder: report of a new family. Eur J Dermatol EJD 18:102–103. doi: 10.1684/ejd.2007.0336 PubMedCrossRefGoogle Scholar
  182. 182.
    Bogunovic D, Byun M, Durfee LA, Abhyankar A, Sanal O, Mansouri D et al (2012) Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency. Science 337:1684–1688. doi: 10.1126/science.1224026 PubMedPubMedCentralCrossRefGoogle Scholar
  183. 183.
    Zhang X, Bogunovic D, Payelle-Brogard B, Francois-Newton V, Speer SD, Yuan C et al (2015) Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation. Nature 517:89–93. doi: 10.1038/nature13801 PubMedCrossRefGoogle Scholar
  184. 184.
    Meuwissen MEC, Schot R, Buta S, Oudesluijs G, Tinschert S, Speer SD et al (2016) Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome. J Exp Med 213:1163–1174. doi: 10.1084/jem.20151529 PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    Bulua AC, Mogul DB, Aksentijevich I, Singh H, He DY, Muenz LR et al (2012) Efficacy of etanercept in the tumor necrosis factor receptor-associated periodic syndrome: a prospective, open-label, dose-escalation study. Arthritis Rheum 64:908–913. doi: 10.1002/art.33416 PubMedCrossRefGoogle Scholar
  186. 186.
    Rebelo SL, Bainbridge SE, Amel-Kashipaz MR, Radford PM, Powell RJ, Todd I et al (2006) Modeling of tumor necrosis factor receptor superfamily 1A mutants associated with tumor necrosis factor receptor-associated periodic syndrome indicates misfolding consistent with abnormal function. Arthritis Rheum 54:2674–2687. doi: 10.1002/art.21964 PubMedCrossRefGoogle Scholar
  187. 187.
    Hull KM, Drewe E, Aksentijevich I, Singh HK, Wong K, McDermott EM et al (2002) The TNF receptor-associated periodic syndrome (TRAPS): emerging concepts of an autoinflammatory disorder. Medicine (Baltimore) 81:349–368CrossRefGoogle Scholar
  188. 188.
    Lainka E, Neudorf U, Lohse P, Timmann C, Stojanov S, Huss K et al (2009) Incidence of TNFRSF1A mutations in German children: epidemiological, clinical and genetic characteristics. Rheumatol Oxf Engl 48:987–991. doi: 10.1093/rheumatology/kep140 CrossRefGoogle Scholar
  189. 189.
    Gattorno M, Pelagatti MA, Meini A, Obici L, Barcellona R, Federici S et al (2008) Persistent efficacy of anakinra in patients with tumor necrosis factor receptor-associated periodic syndrome. Arthritis Rheum 58:1516–1520. doi: 10.1002/art.23475 PubMedCrossRefGoogle Scholar
  190. 190.
    Sacré K, Brihaye B, Lidove O, Papo T, Pocidalo M-A, Cuisset L et al (2008) Dramatic improvement following interleukin 1beta blockade in tumor necrosis factor receptor-1-associated syndrome (TRAPS) resistant to anti-TNF-alpha therapy. J Rheumatol 35:357–358PubMedGoogle Scholar
  191. 191.
    Grimwood C, Despert V, Jeru I, Hentgen V (2015) On-demand treatment with anakinra: a treatment option for selected TRAPS patients. Rheumatol Oxf Engl 54:1749–1751. doi: 10.1093/rheumatology/kev111 CrossRefGoogle Scholar
  192. 192.
    Bulua AC, Simon A, Maddipati R, Pelletier M, Park H, Kim K-Y et al (2011) Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS). J Exp Med 208:519–533. doi: 10.1084/jem.20102049 PubMedPubMedCentralCrossRefGoogle Scholar
  193. 193.
    Borghini S, Ferrera D, Prigione I, Fiore M, Ferraris C, Mirisola V et al (2016) Gene expression profile in TNF receptor-associated periodic syndrome reveals constitutively enhanced pathways and new players in the underlying inflammation. Clin Exp Rheumatol 34:S121–S128PubMedGoogle Scholar
  194. 194.
    Jéru I, Cochet E, Duquesnoy P, Hentgen V, Copin B, Mitjavila-Garcia MT et al (2014) Brief report: involvement of TNFRSF11A molecular defects in autoinflammatory disorders. Arthritis Rheumatol Hoboken NJ 66:2621–2627. doi: 10.1002/art.38727 CrossRefGoogle Scholar
  195. 195.
    Blaydon DC, Biancheri P, Di W-L, Plagnol V, Cabral RM, Brooke MA et al (2011) Inflammatory skin and bowel disease linked to ADAM17 deletion. N Engl J med 365:1502–1508. doi: 10.1056/NEJMoa1100721 PubMedCrossRefGoogle Scholar
  196. 196.
    Hu H, Sun S-C (2016) Ubiquitin signaling in immune responses. Cell res 26:457–483. doi: 10.1038/cr.2016.40 PubMedPubMedCentralCrossRefGoogle Scholar
  197. 197.
    Cohen P (2014) Immune diseases caused by mutations in kinases and components of the ubiquitin system. Nat Immunol 15:521–529. doi: 10.1038/ni.2892 PubMedPubMedCentralCrossRefGoogle Scholar
  198. 198.
    Zhou Q, Wang H, Schwartz DM, Stoffels M, Park YH, Zhang Y et al (2016) Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease. Nat Genet 48:67–73. doi: 10.1038/ng.3459 PubMedCrossRefGoogle Scholar
  199. 199.
    Shigemura T, Kaneko N, Kobayashi N, Kobayashi K, Takeuchi Y, Nakano N et al (2016) Novel heterozygous C243Y A20/TNFAIP3 gene mutation is responsible for chronic inflammation in autosomal-dominant Behçet’s disease. RMD Open 2:e000223. doi: 10.1136/rmdopen-2015-000223 PubMedPubMedCentralCrossRefGoogle Scholar
  200. 200.
    Ohnishi H, Kawamoto N, Seishima M, Ohara O, Fukao T (2017) A Japanese family case with juvenile onset Behçet’s disease caused by TNFAIP3 mutation. Allergol Int Off J Jpn Soc Allergol 66:146–148. doi: 10.1016/j.alit.2016.06.006 CrossRefGoogle Scholar
  201. 201.
    Wertz IE, O’Rourke KM, Zhou H, Eby M, Aravind L, Seshagiri S et al (2004) De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature 430:694–699. doi: 10.1038/nature02794 PubMedCrossRefGoogle Scholar
  202. 202.
    Vande Walle L, Van Opdenbosch N, Jacques P, Fossoul A, Verheugen E, Vogel P et al (2014) Negative regulation of the NLRP3 inflammasome by A20 protects against arthritis. Nature 512:69–73. doi: 10.1038/nature13322 PubMedCrossRefGoogle Scholar
  203. 203.
    Duong BH, Onizawa M, Oses-Prieto JA, Advincula R, Burlingame A, Malynn BA et al (2015) A20 restricts ubiquitination of pro-interleukin-1β protein complexes and suppresses NLRP3 inflammasome activity. Immunity 42:55–67. doi: 10.1016/j.immuni.2014.12.031 PubMedPubMedCentralCrossRefGoogle Scholar
  204. 204.
    Shimizu Y, Taraborrelli L, Walczak H (2015) Linear ubiquitination in immunity. Immunol Rev 266:190–207. doi: 10.1111/imr.12309 PubMedPubMedCentralCrossRefGoogle Scholar
  205. 205.
    Fiil BK, Gyrd-Hansen M (2014) Met1-linked ubiquitination in immune signalling. FEBS J 281:4337–4350. doi: 10.1111/febs.12944 PubMedPubMedCentralCrossRefGoogle Scholar
  206. 206.
    Elliott PR, Komander D (2016) Regulation of Met1-linked polyubiquitin signalling by the deubiquitinase OTULIN. FEBS J 283:39–53. doi: 10.1111/febs.13547 PubMedCrossRefGoogle Scholar
  207. 207.
    Zhou Q, Yu X, Demirkaya E, Deuitch N, Stone D, Tsai WL et al (2016) Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease. Proc Natl Acad Sci U S A 113:10127–10132. doi: 10.1073/pnas.1612594113 PubMedPubMedCentralCrossRefGoogle Scholar
  208. 208.
    Boisson B, Laplantine E, Prando C, Giliani S, Israelsson E, Xu Z et al (2012) Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency. Nat Immunol 13:1178–1186. doi: 10.1038/ni.2457 PubMedPubMedCentralCrossRefGoogle Scholar
  209. 209.
    Zhou Q, Yang D, Ombrello AK, Zavialov AV, Toro C, Zavialov AV et al (2014) Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med 370:911–920. doi: 10.1056/NEJMoa1307361 PubMedPubMedCentralCrossRefGoogle Scholar
  210. 210.
    Navon Elkan P, Pierce SB, Segel R, Walsh T, Barash J, Padeh S et al (2014) Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. N Engl J Med 370:921–931. doi: 10.1056/NEJMoa1307362 PubMedCrossRefGoogle Scholar
  211. 211.
    Ben-Ami T, Revel-Vilk S, Brooks R, Shaag A, Hershfield MS, Kelly SJ et al (2016) Extending the clinical phenotype of adenosine deaminase 2 deficiency. J Pediatr 177:316–320. doi: 10.1016/j.jpeds.2016.06.058 PubMedCrossRefGoogle Scholar
  212. 212.
    Zavialov AV, Gracia E, Glaichenhaus N, Franco R, Zavialov AV, Lauvau G (2010) Human adenosine deaminase 2 induces differentiation of monocytes into macrophages and stimulates proliferation of T helper cells and macrophages. J Leukoc Biol 88:279–290. doi: 10.1189/jlb.1109764 PubMedCrossRefGoogle Scholar
  213. 213.
    Ombrello MJ, Remmers EF, Sun G, Freeman AF, Datta S, Torabi-Parizi P et al (2012) Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions. N Engl J Med 366:330–338. doi: 10.1056/NEJMoa1102140 PubMedPubMedCentralCrossRefGoogle Scholar
  214. 214.
    Zhou Q, Lee G-S, Brady J, Datta S, Katan M, Sheikh A et al (2012) A hypermorphic missense mutation in PLCG2, encoding phospholipase Cγ2, causes a dominantly inherited autoinflammatory disease with immunodeficiency. Am J Hum Genet 91:713–720. doi: 10.1016/j.ajhg.2012.08.006 PubMedPubMedCentralCrossRefGoogle Scholar
  215. 215.
    Chae JJ, Park YH, Park C, Hwang I-Y, Hoffmann P, Kehrl JH et al (2015) Connecting two pathways through Ca 2+ signaling: NLRP3 inflammasome activation induced by a hypermorphic PLCG2 mutation. Arthritis Rheumatol Hoboken NJ 67:563–567. doi: 10.1002/art.38961 CrossRefGoogle Scholar
  216. 216.
    Wiseman DH, May A, Jolles S, Connor P, Powell C, Heeney MM et al (2013) A novel syndrome of congenital sideroblastic anemia, B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD). Blood 122:112–123. doi: 10.1182/blood-2012-08-439083 PubMedPubMedCentralCrossRefGoogle Scholar
  217. 217.
    Chakraborty PK, Schmitz-Abe K, Kennedy EK, Mamady H, Naas T, Durie D et al (2014) Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD). Blood 124:2867–2871. doi: 10.1182/blood-2014-08-591370 PubMedPubMedCentralCrossRefGoogle Scholar
  218. 218.
    Sasarman F, Thiffault I, Weraarpachai W, Salomon S, Maftei C, Gauthier J et al (2015) The 3′ addition of CCA to mitochondrial tRNASer(AGY) is specifically impaired in patients with mutations in the tRNA nucleotidyl transferase TRNT1. Hum Mol Genet 24:2841–2847. doi: 10.1093/hmg/ddv044 PubMedPubMedCentralCrossRefGoogle Scholar
  219. 219.
    Kaustio M, Haapaniemi E, Göös H, Hautala T, Park G, Syrjänen J et al (2017) Damaging heterozygous mutations in NFKB1 lead to diverse immunological phenotypes. J Allergy Clin Immunol. doi: 10.1016/j.jaci.2016.10.054
  220. 220.
    Schipp C, Nabhani S, Bienemann K, Simanovsky N, Kfir-Erenfeld S, Assayag-Asherie N et al (2016) Specific antibody deficiency and autoinflammatory disease extend the clinical and immunological spectrum of heterozygous NFKB1 loss-of-function mutations in humans. Haematologica 101:e392–e396. doi: 10.3324/haematol.2016.145136 PubMedPubMedCentralCrossRefGoogle Scholar
  221. 221.
    Molho-Pessach V, Lerer I, Abeliovich D, Agha Z, Abu Libdeh A, Broshtilova V et al (2008) The H syndrome is caused by mutations in the nucleoside transporter hENT3. Am J Hum Genet 83:529–534. doi: 10.1016/j.ajhg.2008.09.013 PubMedPubMedCentralCrossRefGoogle Scholar
  222. 222.
    Melki I, Lambot K, Jonard L, Couloigner V, Quartier P, Neven B et al (2013) Mutation in the SLC29A3 gene: a new cause of a monogenic, autoinflammatory condition. Pediatrics 131:e1308–e1313. doi: 10.1542/peds.2012-2255 PubMedCrossRefGoogle Scholar
  223. 223.
    Jordan CT, Cao L, Roberson EDO, Pierson KC, Yang C-F, Joyce CE et al (2012) PSORS2 is due to mutations in CARD14. Am J hum Genet 90:784–795. doi: 10.1016/j.ajhg.2012.03.012 PubMedPubMedCentralCrossRefGoogle Scholar
  224. 224.
    Fuchs-Telem D, Sarig O, van Steensel MAM, Isakov O, Israeli S, Nousbeck J et al (2012) Familial pityriasis rubra pilaris is caused by mutations in CARD14. Am J Hum Genet 91:163–170. doi: 10.1016/j.ajhg.2012.05.010 PubMedPubMedCentralCrossRefGoogle Scholar
  225. 225.
    Eytan O, Sarig O, Sprecher E, van Steensel MA (2014) Clinical response to ustekinumab in familial pityriasis rubra pilaris caused by a novel mutation in CARD14. Br J Dermatol 171:420–422. doi: 10.1111/bjd.12952 PubMedCrossRefGoogle Scholar
  226. 226.
    Setta-Kaffetzi N, Simpson MA, Navarini AA, Patel VM, Lu H-C, Allen MH et al (2014) AP1S3 mutations are associated with pustular psoriasis and impaired toll-like receptor 3 trafficking. Am J hum Genet 94:790–797. doi: 10.1016/j.ajhg.2014.04.005 PubMedPubMedCentralCrossRefGoogle Scholar
  227. 227.
    Mahil SK, Twelves S, Farkas K, Setta-Kaffetzi N, Burden AD, Gach JE et al (2016) AP1S3 mutations cause skin autoinflammation by disrupting keratinocyte autophagy and up-regulating IL-36 production. J Invest Dermatol 136:2251–2259. doi: 10.1016/j.jid.2016.06.618 PubMedPubMedCentralCrossRefGoogle Scholar
  228. 228.
    Gattorno M, Sormani MP, D’Osualdo A, Pelagatti MA, Caroli F, Federici S et al (2008) A diagnostic score for molecular analysis of hereditary autoinflammatory syndromes with periodic fever in children. Arthritis Rheum 58:1823–1832. doi: 10.1002/art.23474 PubMedCrossRefGoogle Scholar
  229. 229.
    Federici S, Gattorno M (2014) A practical approach to the diagnosis of autoinflammatory diseases in childhood. Best Pract Res Clin Rheumatol 28:263–276. doi: 10.1016/j.berh.2014.05.005 PubMedCrossRefGoogle Scholar
  230. 230.
    Moghaddas F, Masters SL (2015) Monogenic autoinflammatory diseases: Cytokinopathies. Cytokine 74:237–246. doi: 10.1016/j.cyto.2015.02.012 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Yvan Jamilloux
    • 1
    • 2
    • 3
  • Alexandre Belot
    • 1
    • 4
  • Flora Magnotti
    • 1
  • Sarah Benezech
    • 1
    • 4
  • Mathieu Gerfaud-Valentin
    • 2
  • Emilie Bourdonnay
    • 1
  • Thierry Walzer
    • 1
  • Pascal Sève
    • 2
  • Thomas Henry
    • 1
  1. 1.CIRI - Centre International de Recherche en Infectiologie, Inserm U1111Université Lyon 1, CNRS UMR5308, ENS LyonLyonFrance
  2. 2.Department of Internal Medicine, Hopital de la Croix Rousse, Hospices Civils de LyonUniversité Lyon 1LyonFrance
  3. 3.Service de Médecine InterneHopital de la Croix-RousseLyonFrance
  4. 4.Department of paediatric rheumatology and nephrology, Hopital Femme-Mère-Enfant, Hospices Civils de LyonUniversité Lyon 1LyonFrance

Personalised recommendations