Skip to main content
SpringerLink
Log in

Autoinflammatory Disorders

  • Chapter
  • First Online:
Cellular Primary Immunodeficiencies

Part of the book series: Rare Diseases of the Immune System ((RDIS))

  • 768 Accesses

Abstract

Autoinflammatory disorders represent an evolving group of conditions which were first mentioned as a separate disease category in 1999, after the genetic basis for tumor necrosis factor (TNF) receptor-associated periodic fever syndrome was identified. Since then, the boundaries of what defines an autoinflammatory condition continue to expand and include diseases which to a varying degree have features of immunodeficiency and classical autoimmunity. There has been considerable progress in mapping the genetic basis of these disorders and understanding the relevant biological pathways responsible for the inflammatory pathology. A targeted therapeutic approach using modern biologicals has in many cases led to significant improvements in disease management and outcomes. According to the latest classification from the International Union of Immunological Societies, there are almost 40 diseases being classed as autoinflammatory. It is beyond the scope of this chapter to describe each condition in detail. Instead, it will shed light on the more common, prototypic, and well-understood conditions which help elucidate autoinflammatory disease pathways in general.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Gül A (2018) Dynamics of inflammatory response in autoinflammatory disorders: autonomous and hyperinflammatory states. Front Immunol 9:2422

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Ben-Chetrit E, Gattorno M, Gul A, Kastner DL, Lachmann HJ, Touitou I et al (2018) Consensus proposal for taxonomy and definition of the autoinflammatory diseases (AIDS): a Delphi study. Ann Rheum Dis 77(11):1558–1565

    Article  CAS  PubMed  Google Scholar 

  3. 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 110(35):14408–14413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chavarría-Smith J, Vance RE (2013) Direct proteolytic cleavage of NLRP1B is necessary and sufficient for inflammasome activation by anthrax lethal factor. PLoS Pathog 9(6):e1003452

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. 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(9):1583–1589

    Article  PubMed  CAS  Google Scholar 

  6. Bernot A, Clepet C, Dasilva C, Devaud C, Petit JL, Caloustian C et al (1997) A candidate gene for familial Mediterranean fever. Nat Genet 17(1):25–31

    Article  Google Scholar 

  7. Aksentijevich I, Centola M, Deng Z, Sood R, Balow JE, Wood G et al (1997) Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial mediterranean fever The International FMF Consortium* Introduction Group 4. Cell 90(4):797–807

    Article  Google Scholar 

  8. Jamilloux Y, Magnotti F, Belot A, Henry T (2018) The pyrin inflammasome: From sensing RhoA GTPases-inhibiting toxins to triggering autoinflammatory syndromes. Pathog Dis 76(3):1–9

    Article  CAS  Google Scholar 

  9. Wise CA (2002) Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder. Hum Mol Genet 11(8):961–969

    Article  CAS  PubMed  Google Scholar 

  10. Shinar Y, Tohami T, Livneh A, Schiby G, Hirshberg A, Nagar M et al (2015) Acquired familial Mediterranean fever associated with a somatic MEFV mutation in a patient with JAK2 associated post-polycythemia myelofibrosis. Orphanet J Rare Dis 10(1):1–6

    Article  Google Scholar 

  11. Balcı-Peynircioğlu B, Kaya-Akça Ü, Arıcı ZS, Avcı E, Akkaya-ulum ZY, Karadağ Ö et al (2020) Comorbidities in familial Mediterranean fever: analysis of 2000 genetically confirmed patients. Rheumatology 59(6):1372–1380

    Article  PubMed  Google Scholar 

  12. 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(10):1879–1885

    Article  CAS  PubMed  Google Scholar 

  13. Goldfinger SE (1972) Colchicine for familial mediterranean fever. N Engl J Med 287(25):1302–1302. https://doi.org/10.1056/NEJM197212212872514

    Article  CAS  PubMed  Google Scholar 

  14. Zemer D, Revach M, Pras M, Modan B, Schor S, Sohar E et al (1974) A controlled trial of colchicine in preventing attacks of familial Mediterranean fever. N Engl J Med 291(18):932–934. https://doi.org/10.1056/NEJM197410312911803

    Article  CAS  PubMed  Google Scholar 

  15. Goldstein RC, Schwabe AD (1974) Prophylactic colchicine therapy in familial Mediterranean fever. A controlled, double-blind study. Ann Intern Med 81(6):792–794

    Article  CAS  PubMed  Google Scholar 

  16. Dinarello CA, van der Meer JWM (2013) Treating inflammation by blocking interleukin-1 in humans. Semin Immunol 25(6):469–484. https://doi.org/10.1016/j.smim.2013.10.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. De Benedetti F, Gattorno M, Anton J, Ben-Chetrit E, Frenkel J, Hoffman HM et al (2018) Canakinumab for the treatment of autoinflammatory recurrent fever syndromes. N Engl J Med 378(20):1908–1919. https://doi.org/10.1056/NEJMoa1706314

    Article  PubMed  Google Scholar 

  18. Moghaddas F, Llamas R, De Nardo D, Martinez-Banaclocha H, Martinez-Garcia JJ, Mesa-Del-Castillo P et al (2017) A novel pyrin-associated autoinflammation with neutrophilic dermatosis mutation further defines 14-3-3 binding of pyrin and distinction to familial Mediterranean fever. Ann Rheum Dis 76(12):2085–2094

    Article  CAS  PubMed  Google Scholar 

  19. Unless R, Act P, Rose W, If T, Rose W, Masters SL et al (2016) Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation. Sci Transl Med 8(332):1–10. Available from: http://eprints.whiterose.ac.uk/98758/

    Google Scholar 

  20. Hong Y, ASI S, Nanthapisal S, Sebire N, Jolles S, Omoyinmi E et al (2019) Autoinflammation due to homozygous S208 MEFV mutation. Ann Rheum Dis 78(4):571–573. Available from: https://ard.bmj.com/content/early/2018/10/24/annrheumdis-2018-214102

    Article  CAS  PubMed  Google Scholar 

  21. 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(8):914–921

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Simon A, Kremer HPH, Wevers RA, Scheffer H, De Jong JG, Van Der Meer JWM et al (2004) Mevalonate kinase deficiency: evidence for a phenotypic continuum. Neurology 62(6):994–997. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15037710

    Article  CAS  PubMed  Google Scholar 

  23. Cuisset L, Drenth JPH, Simon A, Vincent MF, Van Der Velde Visser S, Van Der Meer JWM et al (2001) Molecular analysis of MVK mutations and enzymatic activity in hyper-IgD and periodic fever syndrome. Eur J Hum Genet 9(4):260–266

    Article  CAS  PubMed  Google Scholar 

  24. 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(2):175–177

    Article  CAS  PubMed  Google Scholar 

  25. Hoffmann GF, Charpentier C, Mayatepek E, Mancini J, Leichsenring M, Gibson KM et al (1993) Clinical and biochemical phenotype in 11 patients with mevalonic aciduria. Pediatrics 91(5):915–921

    Article  CAS  PubMed  Google Scholar 

  26. Ter Haar NM, Oswald M, Jeyaratnam J, Anton J, Barron KS, Brogan PA et al (2015) Recommendations for the management of autoinflammatory diseases. Ann Rheum Dis 74(9):1636–1644

    Article  PubMed  CAS  Google Scholar 

  27. Bodar EJ, van der Hilst JCH, Drenth JPH, van der Meer JWM, Simon A (2005) Effect of etanercept and anakinra on inflammatory attacks in the hyper-IgD syndrome: Introducing a vaccination provocation model. Neth J Med 63(7):260–264

    CAS  PubMed  Google Scholar 

  28. Tsitsami E, Papadopoulou C, Speletas MA (2013) Case of Hyperimmunoglobulinemia D Syndrome Successfully Treated with Canakinumab. Case Rep Rheumatol 2013:1–4

    Google Scholar 

  29. Curtis CD, Fox CC (2015) Treatment of adult hyper-IgD syndrome with canakinumab. J Allergy Clin Immunol Pract 3(5):817–818

    Article  PubMed  Google Scholar 

  30. Arostegui JI, Anton J, Calvo I, Robles A, Iglesias E, Lopez-Montesinos B et al (2017 Aug) Open-Label, Phase II Study to assess the efficacy and safety of Canakinumab treatment in active hyperimmunoglobulinemia D with periodic fever syndrome. Arthritis Rheumatol 69(8):1679–1688

    Article  CAS  PubMed  Google Scholar 

  31. Demirkaya E, Caglar MK, Waterham HR, Topaloglu R, Ozen S (2007) A patient with hyper-IgD syndrome responding to anti-TNF treatment. Clin Rheumatol 26(10):1757–1759

    Article  PubMed  Google Scholar 

  32. Topaloǧlu R, Ayaz NA, Waterham HR, Yüce A, Gumruk F, Sanal Ö, Hyperimmunoglobulinemia D (2008) periodic fever syndrome; treatment with etanercept and follow-up. Clin Rheumatol 27(10):1317–1320

    Article  PubMed  Google Scholar 

  33. Shendi HM, Devlin LA, Edgar JD (2014) Interleukin 6 blockade for hyperimmunoglobulin d and periodic fever syndrome. J Clin Rheumatol 20(2):103–105

    Article  PubMed  Google Scholar 

  34. Arkwright PD, Abinun M, Cant AJ (2007) Mevalonic aciduria cured by bone marrow transplantation. N Engl J Med 357(13):1350–1350. https://doi.org/10.1056/NEJMc072018

    Article  CAS  PubMed  Google Scholar 

  35. Neven B, Valayannopoulos V, Quartier P, Blanche S, Prieur A-M, Debré M et al (2007) Allogeneic bone marrow transplantation in mevalonic aciduria. N Engl J Med 356(26):2700–2703. https://doi.org/10.1056/NEJMoa070715

    Article  CAS  PubMed  Google Scholar 

  36. Pelegrín P (2011) Inflammasome activation by danger signals. In: The inflammasomes. Springer, Basel

    Google Scholar 

  37. Saito M, Nishikomori R, Kambe N, Fujisawa A, Tanizaki H, Takeichi K et al (2008) Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients. Blood 111(4):2132–2141. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18063752

    Article  CAS  PubMed  Google Scholar 

  38. Zhou Q, Aksentijevich I, Wood GM, Walts AD, Hoffmann P, Remmers EF et al (2015) Cryopyrin-associated periodic syndrome caused by a myeloid-restricted somatic NLRP3 mutation. Arthritis Rheumatol 67(9):2482–2486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Rowczenio DM, Gomes SM, Aróstegui JI, Mensa-Vilaro A, Omoyinmi E, Trojer H et al (2017) Late-onset cryopyrin-associated periodic syndromes caused by somatic NLRP3 mosaicism-UK single center experience. Front Immunol 8:1410

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. 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(3):301–305. Available from: http://www.nature.com/articles/ng756z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Aksentijevich I, Putnam CD, Remmers EF, Mueller JL, Le J, Kolodner RD et al (2007) The clinical continuum of cryopyrinopathies: Novel CIAS1 mutations in North American patients and a new cryopyrin model. Arthritis Rheum 56(4):1273–1285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Goldbach-Mansky R (2011) Current status of understanding the pathogenesis and management of patients with NOMID/CINCA. Curr Rheumatol Rep 13(2):123–131

    Article  PubMed  PubMed Central  Google Scholar 

  43. Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, Kone-Paut I, Goldbach-Mansky R, Lachmann H et al (2017) Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS). Ann Rheum Dis 76(6):942–947. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27707729

    Article  PubMed  Google Scholar 

  44. Neven B, Marvillet I, Terrada C, Ferster A, Boddaert N, Couloignier V et al (2010) Long-term efficacy of the interleukin-1 receptor antagonist anakinra in ten patients with neonatal-onset multisystem inflammatory disease/chronic infantile neurologic, cutaneous, articular syndrome. Arthritis Rheum 62(1):258–267

    Article  CAS  PubMed  Google Scholar 

  45. Kuemmerle-Deschner JB, Wittkowski H, Tyrrell PN, Koetter I, Lohse P, Ummenhofer K et al (2013) Treatment of Muckle-Wells syndrome: analysis of two IL-1-blocking regimens. Arthritis Res Ther 15(3):1–8

    Article  CAS  Google Scholar 

  46. Canna SW, Girard C, Malle L, de Jesus A, Romberg N, Kelsen J et al (2017) Life-threatening NLRC4-associated hyperinflammation successfully treated with IL-18 inhibition. J Allergy Clin Immunol 139(5):1698–1701. Available from: https://www.sciencedirect.com/science/article/pii/S0091674916313525

    Article  CAS  PubMed  Google Scholar 

  47. 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(10):1140–1146. Available from: http://www.nature.com/articles/ng.3089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. 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(10):1135–1139. Available from: http://www.nature.com/articles/ng.3066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. 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(1):244–248

    Article  CAS  PubMed  Google Scholar 

  50. 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 69(2):447–459

    Article  CAS  PubMed  Google Scholar 

  51. 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(5):1614–1619

    Article  PubMed  PubMed Central  Google Scholar 

  52. Grandemange S, Sanchez E, Louis-Plence P, Tran Mau-Them F, Bessis D, Coubes C et al (2017) A new autoinflammatory and autoimmune syndrome associated with NLRP1 mutations: NAIAD (NLRP1- associated autoinflammation with arthritis and dyskeratosis). Ann Rheum Dis 76(7):1191–1198

    Article  CAS  PubMed  Google Scholar 

  53. 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(1):67–73. Available from: http://www.nature.com/articles/ng.3459

    Article  CAS  PubMed  Google Scholar 

  54. Matmati M, Jacques P, Maelfait J, Verheugen E, Kool M, Sze M et al (2011) A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis. Nat Genet 43(9):908–912. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21841782

    Article  CAS  PubMed  Google Scholar 

  55. Lawless D, Pathak S, Scambler TE, Ouboussad L, Anwar R (2018) Savic S. A case of adult-Onset Still’s disease caused by a novel splicing mutation in TNFAIP3 successfully treated with tocilizumab. Front Immunol 9:1–8

    Article  CAS  Google Scholar 

  56. Takagi M, Ogata S, Ueno H, Yoshida K, Yeh T, Hoshino A et al (2017) Haploinsufficiency of TNFAIP3 (A20) by germline mutation is involved in autoimmune lymphoproliferative syndrome. J Allergy Clin Immunol 139(6):1914–1922. https://doi.org/10.1016/j.jaci.2016.09.038

    Article  CAS  PubMed  Google Scholar 

  57. Aeschlimann FA, Batu ED, Canna SW, Go E, Gül A, Hoffmann P et al (2018) A20 haploinsufficiency (HA20): Clinical phenotypes and disease course of patients with a newly recognised NF-kB-mediated autoinflammatory disease. Ann Rheum Dis 77(5):728–735. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29317407

    Article  CAS  PubMed  Google Scholar 

  58. Mulhern CM, Hong Y, Omoyinmi E, Jacques TS, D’Arco F, Hemingway C et al (2019) Janus kinase 1/2 inhibition for the treatment of autoinflammation associated with heterozygous TNFAIP3 mutation. J Allergy Clin Immunol 144(3):863–866. e5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Damgaard RB, Walker JA, Marco-Casanova P, Morgan NV, Titheradge HL, Elliott PR et al (2016) The Deubiquitinase OTULIN is an essential negative regulator of inflammation and autoimmunity. Cell 166(5):1215–1230.e20. https://doi.org/10.1016/j.cell.2016.07.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. 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 113(36):10127–10132. https://doi.org/10.1073/pnas.1612594113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Hayden MS, Ghosh S (2012) NF-κB, the first quarter-century: remarkable progress and outstanding questions. Genes Dev 26(3):203–234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Badran YR, Dedeoglu F, Leyva Castillo JM, Bainter W, Ohsumi TK, Bousvaros A et al (2017) Human RELA haploinsufficiency results in autosomal-dominant chronic mucocutaneous ulceration. J Exp Med 214(7):1937–1947. https://doi.org/10.1084/jem.20160724

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Comrie WA, Faruqi AJ, Price SR, Zhang Y, Koneti Rao V, Su HC et al (2018) RELA haploinsufficiency in CD4 lymphoproliferative disease with autoimmune cytopenias. J Allergy Clin Immunol 141(4):1507–1510. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0091674917330117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Crow YJ (2011) Type I interferonopathies: a novel set of inborn errors of immunity. Ann N Y Acad Sci 1238(1):91–98

    Article  CAS  PubMed  Google Scholar 

  65. Lee-Kirsch MA, Wolf C, Kretschmer S, Roers A (2015) Type I interferonopathies—an expanding disease spectrum of immunodysregulation. Semin Immunopathol 37(4):349–357

    Article  CAS  PubMed  Google Scholar 

  66. Crow YJ, Rehwinkel J (2009) Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity. Hum Mol Genet 18(R2):130–136

    Article  CAS  Google Scholar 

  67. 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(5):503–509. Available from: http://www.nature.com/articles/ng.2933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Crow YJ, Chase DS, Lowenstein Schmidt J, Szynkiewicz M, Forte GMA, Gornall HL et al (2015) Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. Am J Med Genet Part A 167(2):296–312. https://doi.org/10.1002/ajmg.a.36887

    Article  CAS  Google Scholar 

  69. Liu Y, Jesus AA, Marrero B, Yang D, Ramsey SE, Sanchez GAM et al (2014) Activated STING in a vascular and pulmonary syndrome. N Engl J Med 371(6):507–518. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25029335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Jeremiah N, Neven B, Gentili M, Callebaut I, Maschalidi S, Stolzenberg M et al (2014) Inherited STING-activating mutation underlies a familial inflammatory. J Clin Invest 124(12):5516–5520

    Article  PubMed  PubMed Central  Google Scholar 

  71. Omoyinmi E, Melo Gomes S, Nanthapisal S, Woo P, Standing A, Eleftheriou D et al (2015) Stimulator of interferon genes-associated vasculitis of infancy. Arthritis Rheumatol 67(3):808

    Article  PubMed  Google Scholar 

  72. Brehm A, Liu Y, Sheikh A, Marrero B, Omoyinmi E, Zhou Q et al (2016) Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production. J Clin Invest 126(2):795–795

    Article  PubMed  PubMed Central  Google Scholar 

  73. 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(6):866–872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Montealegre Sanchez GA, Reinhardt A, Ramsey S, Wittkowski H, Hashkes PJ, Berkun Y et al (2018) JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies. J Clin Invest 128(7):3041–3052. https://doi.org/10.1172/JCI98814

    Article  Google Scholar 

  75. Rodero MP, Tesser A, Bartok E, Rice GI, Della Mina E, Depp M et al (2017) Type i interferon-mediated autoinflammation due to DNase II deficiency. Nat Commun 8(1):1–15

    Article  CAS  Google Scholar 

  76. Hashkes PJ, Laxer RM (2019) Textbook of autoinflammation. Springer International Publishing, Cham, Switzerland, Chapter 18, pages 329–345

    Google Scholar 

  77. https://www.printo.it/eurofever/autoinflammatory_diseases.asp. Eurofever Project [Internet]. [cited 2020 Feb 18]. Available from: https://www.printo.it/eurofever/

  78. Pelagatti MA, Meini A, Caorsi R, Cattalini M, Federici S, Zulian F et al (2011) Long-term clinical Profile of children with the low-penetrance R92Q mutation of the tNFRSF1A gene. Arthritis Rheum 63(4):1141–1150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Jawaheer D, Seldin MF, Amos CI, Chen WV, Shigeta R, Monteiro J et al (2001) A Genomewide screen in multiplex rheumatoid arthritis families suggests genetic overlap with other autoimmune diseases. Am J Hum Genet 68(4):927–936

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Direskeneli H, Saruhan-Direskeneli G, Amoura Z, Dode C, Wechsler B, Piette JC (2005) R92Q TNFRSF1A mutation and Behçet’s disease: Comment on the article by Amoura et al. [5] (multiple letters). Arthritis Rheum 52(8):2583–2584

    Article  PubMed  Google Scholar 

  81. 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(5):1516–1520

    Article  CAS  PubMed  Google Scholar 

  82. 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(3):908–913

    Article  CAS  PubMed  Google Scholar 

  83. Nedjai B, Hitman GA, Quillinan N, Coughlan RJ, Church L, McDermott MF et al (2009) Proinflammatory action of the antiinflammatory drug infliximab in tumor necrosis factor receptor-associated periodic syndrome. Arthritis Rheum 60(2):619–625

    Article  CAS  PubMed  Google Scholar 

  84. Vaitla PM, Radford PM, Tighe PJ, Powell RJ, McDermott EM, Todd I et al (2011) Role of interleukin-6 in a patient with tumor necrosis factor receptor-associated periodic syndrome. Arthritis Rheum 63(4):1151–1155

    Article  PubMed  Google Scholar 

  85. 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(23):2438–2444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. 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(23):2426–2437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Thacker PG, Binkovitz LA, Thomas KB (2012) Deficiency of interleukin-1-receptor antagonist syndrome: a rare auto-inflammatory condition that mimics multiple classic radiographic findings. Pediatr Radiol 42(4):495–498

    Article  PubMed  Google Scholar 

  88. Gabay C, Towne JE (2015) Regulation and function of interleukin-36 cytokines in homeostasis and pathological conditions. J Leukoc Biol 97(4):645–652

    Article  CAS  PubMed  Google Scholar 

  89. Marrakchi S, Guigue P, Renshaw BR, Puel A, Pei XY, Fraitag S et al (2011) Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med 365(7):620–628

    Article  CAS  PubMed  Google Scholar 

  90. Onoufriadis A, Simpson MA, Pink AE, Di Meglio P, Smith CH, Pullabhatla V et al (2011) Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis. Am J Hum Genet [Internet] 89(3):432–437. https://doi.org/10.1016/j.ajhg.2011.07.022

    Article  CAS  Google Scholar 

  91. De Inocencio J, Mensa-Vilaro A, Tejada-Palacios P, Enriquez-Merayo E, González-Roca E, Magri G et al (2015) Somatic NOD2 mosaicism in Blau syndrome. J Allergy Clin Immunol 136(2):484–487. e2

    Article  PubMed  PubMed Central  Google Scholar 

  92. Rosé CD, Doyle TM, McIlvain-Simpson G, Coffman JE, Rosenbaum JT, Davey MP et al (2005) Blau syndrome mutation of CARD15/NOD2 in sporadic early onset granulomatous arthritis. J Rheumatol 32(2):373–375

    PubMed  Google Scholar 

  93. Sarens IL, Casteels I, Anton J, Bader-Meunier B, Brissaud P, Chédeville G et al (2018) Blau syndrome–associated uveitis: preliminary results from an international prospective interventional case series. Am J Ophthalmol 187:158–166

    Article  PubMed  Google Scholar 

  94. Saini SK, Rose CD (1996) Liver involvement in familial granulomatous arthritis (Blau syndrome). J Rheumatol [Internet] 23(2):396–399. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8882056

    CAS  Google Scholar 

  95. Aróstegui JI, Arnal C, Merino R, Modesto C, Carballo MA, 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(11):3805–3813

    Article  PubMed  CAS  Google Scholar 

  96. Becker ML, Martin TM, Doyle TM, Rosé CD (2007) Interstitial pneumonitis in Blau syndrome with documented mutation in CARD15. Arthritis Rheum 56(4):1292–1294

    Article  CAS  PubMed  Google Scholar 

  97. See Ting S, Ziegler J, Fischer E (1998) Familial granulomatous arthritis (Blau syndrome) with granulomatous renal lesions. J Pediatr 133(3):450–452

    Article  Google Scholar 

  98. Milman N, Andersen CB, Hansen A, Van Overeem Hansen T, Nielsen FC, Fledelius H et al (2006) Favourable effect of TNF-α inhibitor (infliximab) on Blau syndrome in monozygotic twins with a de novo CARD15 mutation. APMIS 114(12):912–919

    Article  PubMed  Google Scholar 

  99. Simonini G, Xu Z, Caputo R, De Libero C, Pagnini I, Pascual V et al (2013) Clinical and transcriptional response to the long-acting interleukin-1 blocker canakinumab in Blau syndrome-related uveitis. Arthritis Rheum 65(2):513–518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Lu L, Shen M, Jiang D, Li Y, Zheng X, Li Y et al (2018) Blau syndrome with good reponses to Tocilizumab: a case report and focused literature review. Semin Arthritis Rheum 47(5):727–731

    Article  PubMed  Google Scholar 

  101. 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 (United Kingdom) 54(6):1008–1016

    Google Scholar 

  102. 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 67(1):288–295

    Article  CAS  PubMed  Google Scholar 

  103. Li Y, Führer M, Bahrami E, Socha P, Klaudel-Dreszler M, Bouzidi A et al (2019) Human RIPK1 deficiency causes combined immunodeficiency and inflammatory bowel diseases. Proc Natl Acad Sci 116(3):970–975. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30591564

    Article  CAS  PubMed  Google Scholar 

  104. Cuchet-Lourenço D, Eletto D, Wu C, Plagnol V, Papapietro O, Curtis J et al (2018) Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation. Science 361(6404):810–813. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30026316

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Tao P, Sun J, Wu Z, Wang S, Wang J, Li W et al (2020) A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1. Nature [Internet] 577(7788):109–114. https://doi.org/10.1038/s41586-019-1830-y

    Article  CAS  Google Scholar 

  106. Lalaoui N, Boyden SE, Oda H, Wood GM, Stone DL, Chau D et al (2020) Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease. Nature [Internet] 577(7788):103–108. https://doi.org/10.1038/s41586-019-1828-5

    Article  CAS  Google Scholar 

  107. Israël A (2010) The IKK complex, a central regulator of NF-kappaB activation. Cold Spring Harb Perspect Biol 2(3):a000158

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  108. Takada H, Nomura A, Ishimura M, Ichiyama M, Ohga S, Hara T (2010) NEMO mutation as a cause of familial occurrence of Behçet’s disease in female patients. Clin Genet 78(6):575–579

    Article  CAS  PubMed  Google Scholar 

  109. Döffinger R, Smahi A, Bessia C, Geissmann F, Feinberg J, Durandy A et al (2001) X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-κB signaling. Nat Genet 27(3):277–285

    Article  PubMed  Google Scholar 

  110. Hanson EP, Monaco-Shawver L, Solt LA, Madge LA, Banerjee PP, May MJ et al (2008) Hypomorphic NEMO mutation database and reconstitution system identifies phenotypic and immunologic diversity. J Allergy Clin Immunol 122(6):1169–1177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Orange JS, Geha RS (2003) Finding NEMO: genetic disorders of NF-κB activation. J Clin Invest 112(7):983–985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Miot C, Imai K, Imai C, Mancini AJ, Kucuk ZY, Kawai T et al (2017) Hematopoietic stem cell transplantation in 29 patients hemizygous for hypomorphic IKBKG/NEMO mutations. Blood 130(12):1456–1467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Mizukami T, Obara M, Nishikomori R, Kawai T, Tahara Y, Sameshima N et al (2012) Successful treatment with infliximab for inflammatory colitis in a patient with X-linked anhidrotic ectodermal dysplasia with immunodeficiency. J Clin Immunol 32(1):39–49

    Article  PubMed  Google Scholar 

  114. Klemann C, Pannicke U, Morris-Rosendahl DJ, Vlantis K, Rizzi M, Uhlig H et al (2016) Transplantation from a symptomatic carrier sister restores host defenses but does not prevent colitis in NEMO deficiency. Clin Immunol 164:52–56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. 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(12):1178–1186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Tuijnenburg P, Lango Allen H, Burns SO, Greene D, Jansen MH, Staples E et al (2018) Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans. J Allergy Clin Immunol 142(4):1285–1296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Kaustio M, Haapaniemi E, Göös H, Hautala T, Park G, Syrjänen J et al (2017) Damaging heterozygous mutations in NFKB1 lead to diverse immunologic phenotypes. J Allergy Clin Immunol 140(3):782–796

    Article  CAS  PubMed  Google Scholar 

  118. Elkan PN, 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(10):921–931

    Article  CAS  Google Scholar 

  119. 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(2):279–290

    Article  CAS  PubMed  Google Scholar 

  120. 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 [Internet] 370(10):911–920. https://doi.org/10.1056/NEJMoa1307361

    Article  CAS  PubMed Central  Google Scholar 

  121. Caorsi R, Penco F, Grossi A, Insalaco A, Omenetti A, Alessio M et al (2017) ADA2 deficiency (DADA2) as an unrecognised cause of early onset polyarteritis nodosa and stroke: a multicentre national study. Ann Rheum Dis 76(10):1648–1656

    Article  CAS  PubMed  Google Scholar 

  122. Schepp J, Proietti M, Frede N, Buchta M, Hübscher K, Rojas Restrepo J et al (2017) Screening of 181 patients with antibody deficiency for deficiency of adenosine deaminase 2 sheds new light on the disease in adulthood. Arthritis Rheumatol 69(8):1689–1700

    Article  CAS  PubMed  Google Scholar 

  123. Hashem H, Kumar AR, Müller I, Babor F, Bredius R, Dalal J et al (2017) Hematopoietic stem cell transplantation rescues the hematological, immunological, and vascular phenotype in DADA2. Blood 130(24):2682–2688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Ombrello AK, Qin J, Hoffmann PM, Kumar P, Stone D, Jones A, Romeo T, Barham B, Pinto-Patarroyo G, Toro C, Soldatos A (2019) Treatment strategies for deficiency of adenosine deaminase 2. N Engl J Med 380(16):1582–1584

    Article  PubMed  PubMed Central  Google Scholar 

  125. Gresset A, Hicks SN, Harden TK, Sondek J (2010) Mechanism of phosphorylation-induced activation of phospholipase C-γ isozymes. J Biol Chem 285(46):35836–35847

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. 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(4):330–338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Morán-Villaseñor E, Saez-de-Ocariz M, Torrelo A, Arostegui JI, Yamazaki-Nakashimada MA, Alcántara-Ortigoza MA et al (2019) Expanding the clinical features of autoinflammation and phospholipase Cγ2-associated antibody deficiency and immune dysregulation by description of a novel patient. J Eur Acad Dermatol Venereol 33(12):2334–2339

    Article  PubMed  CAS  Google Scholar 

  128. Neves JF, Doffinger R, Barcena-Morales G, Martins C, Papapietro O, Plagnol V et al (2018) Novel PLCG2 Mutation in a patient with APLAID and Cutis Laxa. Front Immunol 9:2863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Zhou Q, Lee GS, 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 [Internet] 91(4):713–720. https://doi.org/10.1016/j.ajhg.2012.08.006

    Article  CAS  Google Scholar 

  130. Novice T, Kariminia A, Del Bel KL, Lu H, Sharma M, Lim CJ et al (2019) A germline mutation in the C2 domain of PLCγ2 associated with gain-of-function expands the phenotype for PLCG2-related diseases. J Clin Immunol 40(2):267–276

    Article  PubMed  CAS  Google Scholar 

  131. 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 [Internet] 214(1):59–71. https://doi.org/10.1084/jem.20161228

    Article  CAS  Google Scholar 

  132. Kile BT, Panopoulos AD, Stirzaker RA, Hacking DF, Tahtamouni LH, Willson TA et al (2007) Mutations in the cofilin partner Aip1/Wdr1 cause autoinflammatory disease and macrothrombocytopenia. Blood 110(7):2371–2380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Brydges SD, Broderick L, McGeough MD, Pena CA, Mueller JL, Hoffman HM (2013) Divergence of IL-1, IL-18, and cell death in NLRP3 inflammasomopathies. J Clin Invest 123(11):4695–4705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Volpi S, Cicalese MP, Tuijnenburg P, Tool ATJ, Cuadrado E, Abu-Halaweh M et al (2019) A combined immunodeficiency with severe infections, inflammation, and allergy caused by ARPC1B deficiency. J Allergy Clin Immunol i:2296–2299

    Article  Google Scholar 

  135. Kahr WHA, Pluthero FG, Elkadri A, Warner N, Drobac M, Chen CH et al (2017) Loss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease. Nat Commun 8:1–14

    Article  CAS  Google Scholar 

  136. 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(1):112–123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Immunology and Allergy, St James’s University Hospital, Leeds, UK

    Mark Kacar & Sinisa Savic

  2. National Institute for Health Research—Leeds Biomedical Research Centre and Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), Wellcome Trust Brenner Building, St James’s University Hospital, Leeds, UK

    Mark Kacar & Sinisa Savic

Authors
  1. Mark Kacar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sinisa Savic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sinisa Savic .

Editor information

Editors and Affiliations

  1. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

    Mario Milco D'Elios

  2. Department of Life Sciences, University of Siena, Siena, Italy

    Cosima Tatiana Baldari

  3. Department of Experimental and Clinical Medicine, University of Florence, Firenze, Florence, Italy

    Francesco Annunziato

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kacar, M., Savic, S. (2021). Autoinflammatory Disorders. In: D'Elios, M.M., Baldari, C.T., Annunziato, F. (eds) Cellular Primary Immunodeficiencies. Rare Diseases of the Immune System. Springer, Cham. https://doi.org/10.1007/978-3-030-70107-9_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-70107-9_11

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-70106-2

  • Online ISBN: 978-3-030-70107-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation