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Defects of the Innate Immune System and Related Immune Deficiencies

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Abstract

The innate immune system is the host’s first line of defense against pathogens. Toll-like receptors (TLRs) are pattern recognition receptors that mediate recognition of pathogen-associated molecular patterns. TLRs also activate signaling transduction pathways involved in host defense, inflammation, development, and the production of inflammatory cytokines. Innate immunodeficiencies associated with defective TLR signaling include mutations in NEMO, IKBA, MyD88, and IRAK4. Other innate immune defects have been associated with susceptibility to herpes simplex encephalitis, viral infections, and mycobacterial disease, as well as chronic mucocutaneous candidiasis and epidermodysplasia verruciformis. Phagocytes and natural killer cells are essential members of the innate immune system and defects in number and/or function of these cells can lead to recurrent infections. Complement is another important part of the innate immune system. Complement deficiencies can lead to increased susceptibility to infections, autoimmunity, or impaired immune complex clearance. The innate immune system must work to quickly recognize and eliminate pathogens as well as coordinate an immune response and engage the adaptive immune system. Defects of the innate immune system can lead to failure to quickly identify pathogens and activate the immune response, resulting in susceptibility to severe or recurrent infections.

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References

  1. Gobin K et al (2017) IRAK4 deficiency in a patient with recurrent pneumococcal infections: case report and review of the literature. Front Pediatr 5:83

    Article  Google Scholar 

  2. Rosenzweig SD, Holland SM (2011) Recent insights into the pathobiology of innate immune deficiencies. Curr Allergy Asthma Rep 11(5):369–377

    Article  CAS  Google Scholar 

  3. Iwasaki A, Medzhitov R (2010) Regulation of adaptive immunity by the innate immune system. Science 327(5963):291–295

    Article  CAS  Google Scholar 

  4. Notarangelo LD (2010) Primary immunodeficiencies. J Allergy Clin Immunol 125(2 Suppl 2):S182–S194

    Article  Google Scholar 

  5. Picard C, Casanova JL, Puel A (2011) Infectious diseases in patients with IRAK-4, MyD88, NEMO, or IkappaBalpha deficiency. Clin Microbiol Rev 24(3):490–497

    Article  CAS  Google Scholar 

  6. Routes J et al (2014) ICON: the early diagnosis of congenital immunodeficiencies. J Clin Immunol 34(4):398–424

    Article  CAS  Google Scholar 

  7. Al-Muhsen S, Casanova JL (2008) The genetic heterogeneity of mendelian susceptibility to mycobacterial diseases. J Allergy Clin Immunol 122(6):1043–1051; quiz 1052–3

  8. Smahi A et al (2000) Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium. Nature 405(6785):466–472

  9. Courtois G et al (2003) A hypermorphic IkappaBalpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency. J Clin Invest 112(7):1108–1115

    Article  CAS  Google Scholar 

  10. Lopez-Granados E et al (2008) A novel mutation in NFKBIA/IKBA results in a degradation-resistant N-truncated protein and is associated with ectodermal dysplasia with immunodeficiency. Hum Mutat 29(6):861–868

    Article  CAS  Google Scholar 

  11. Orange JS et al (2004) The presentation and natural history of immunodeficiency caused by nuclear factor kappaB essential modulator mutation. J Allergy Clin Immunol 113(4):725–733

    Article  CAS  Google Scholar 

  12. Heller S et al (2020) T cell impairment is predictive for a severe clinical course in NEMO deficiency. J Clin Immunol 40(3):421–434

    Article  CAS  Google Scholar 

  13. Hanson EP et al (2008) Hypomorphic nuclear factor-kappaB essential modulator mutation database and reconstitution system identifies phenotypic and immunologic diversity. J Allergy Clin Immunol 122(6):1169–1177 e16

  14. Cheng LE et al (2009) Persistent systemic inflammation and atypical enterocolitis in patients with NEMO syndrome. Clin Immunol 132(1):124–131

    Article  CAS  Google Scholar 

  15. Bonilla FA et al (2005) Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol 94(5 Suppl 1):S1-63

    Article  Google Scholar 

  16. Miot C et al (2017) Hematopoietic stem cell transplantation in 29 patients hemizygous for hypomorphic IKBKG/NEMO mutations. Blood 130(12):1456–1467

    Article  CAS  Google Scholar 

  17. Picard C et al (2010) Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency. Medicine (Baltimore) 89(6):403–425

    Article  CAS  Google Scholar 

  18. Platt CD et al (2019) A novel truncating mutation in MYD88 in a patient with BCG adenitis, neutropenia and delayed umbilical cord separation. Clin Immunol 207:40–42

    Article  CAS  Google Scholar 

  19. Israel L et al (2017) Human adaptive immunity rescues an inborn error of innate immunity. Cell 168(5):789–800 e10

  20. Herman M et al (2012) Heterozygous TBK1 mutations impair TLR3 immunity and underlie herpes simplex encephalitis of childhood. J Exp Med 209(9):1567–1582

    Article  CAS  Google Scholar 

  21. Zhang SY et al (2007) TLR3 deficiency in patients with herpes simplex encephalitis. Science 317(5844):1522–1527

    Article  CAS  Google Scholar 

  22. Guo Y et al (2011) Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity. J Exp Med 208(10):2083–2098

    Article  CAS  Google Scholar 

  23. Gorbea C et al (2010) A role for Toll-like receptor 3 variants in host susceptibility to enteroviral myocarditis and dilated cardiomyopathy. J Biol Chem 285(30):23208–23223

    Article  CAS  Google Scholar 

  24. Casrouge A et al (2006) Herpes simplex virus encephalitis in human UNC-93B deficiency. Science 314(5797):308–312

    Article  CAS  Google Scholar 

  25. Perez de Diego R et al (2010) Human TRAF3 adaptor molecule deficiency leads to impaired Toll-like receptor 3 response and susceptibility to herpes simplex encephalitis. Immunity 33(3):400–411

  26. Sancho-Shimizu V et al (2011) Herpes simplex encephalitis in children with autosomal recessive and dominant TRIF deficiency. J Clin Invest 121(12):4889–4902

    Article  CAS  Google Scholar 

  27. Andersen LL et al (2015) Functional IRF3 deficiency in a patient with herpes simplex encephalitis. J Exp Med 212(9):1371–1379

    Article  CAS  Google Scholar 

  28. Hambleton S et al (2013) STAT2 deficiency and susceptibility to viral illness in humans. Proc Natl Acad Sci USA 110(8):3053–3058

    Article  CAS  Google Scholar 

  29. Picard C et al (2018) International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity. J Clin Immunol 38(1):96–128

    Article  Google Scholar 

  30. Lee-Kirsch MA, Wolf C, Gunther C (2014) Aicardi-Goutieres syndrome: a model disease for systemic autoimmunity. Clin Exp Immunol 175(1):17–24

    Article  CAS  Google Scholar 

  31. Meesilpavikkai K et al (2019) Efficacy of baricitinib in the treatment of chilblains associated with Aicardi-Goutieres syndrome, a type I interferonopathy. Arthritis Rheumatol 71(5):829–831

    Article  Google Scholar 

  32. Fazzi E et al (2013) Aicardi-Goutieres syndrome, a rare neurological disease in children: a new autoimmune disorder? Autoimmun Rev 12(4):506–509

    Article  CAS  Google Scholar 

  33. Briggs TA et al (2016) Spondyloenchondrodysplasia due to mutations in ACP5: a comprehensive survey. J Clin Immunol 36(3):220–234

    Article  CAS  Google Scholar 

  34. Mahdaviani SA et al (2020) Mendelian susceptibility to mycobacterial disease (MSMD): clinical and genetic features of 32 Iranian patients. J Clin Immunol 40(6):872–882

    Article  CAS  Google Scholar 

  35. Bustamante J (2020) Mendelian susceptibility to mycobacterial disease: recent discoveries. Hum Genet 139(6–7):993–1000

    Article  CAS  Google Scholar 

  36. Lee WI et al (2013) Patients with inhibitory and neutralizing auto-antibodies to interferon-gamma resemble the sporadic adult-onset phenotype of Mendelian Susceptibility to Mycobacterial Disease (MSMD) lacking Bacille Calmette-Guerin (BCG)-induced diseases. Immunobiology 218(5):762–771

    Article  CAS  Google Scholar 

  37. de Beaucoudrey L et al (2010) Revisiting human IL-12Rbeta1 deficiency: a survey of 141 patients from 30 countries. Medicine (Baltimore) 89(6):381–402

    Article  Google Scholar 

  38. Chapgier A et al (2009) A partial form of recessive STAT1 deficiency in humans. J Clin Invest 119(6):1502–1514

    Article  CAS  Google Scholar 

  39. Dupuis S et al (2003) Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency. Nat Genet 33(3):388–391

    Article  CAS  Google Scholar 

  40. Bogunovic D et al (2012) Mycobacterial disease and impaired IFN-gamma immunity in humans with inherited ISG15 deficiency. Science 337(6102):1684–1688

    Article  CAS  Google Scholar 

  41. Roesler J et al (2004) Hematopoietic stem cell transplantation for complete IFN-gamma receptor 1 deficiency: a multi-institutional survey. J Pediatr 145(6):806–812

    Article  CAS  Google Scholar 

  42. Toubiana J et al (2016) Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype. Blood 127(25):3154–3164

    Article  CAS  Google Scholar 

  43. Engelhardt KR, Grimbacher B (2012) Mendelian traits causing susceptibility to mucocutaneous fungal infections in human subjects. J Allergy Clin Immunol 129(2):294–305; quiz 306–7

  44. Glocker EO et al (2009) A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N Engl J Med 361(18):1727–1735

    Article  CAS  Google Scholar 

  45. Drewniak A et al (2013) Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency. Blood 121(13):2385–2392

    Article  CAS  Google Scholar 

  46. Queiroz-Telles F et al (2019) Successful allogenic stem cell transplantation in patients with inherited CARD9 deficiency. J Clin Immunol 39(5):462–469

    Article  CAS  Google Scholar 

  47. de Medeiros AK et al (2016) Erratum to: Chronic and invasive fungal infections in a family with CARD9 deficiency. J Clin Immunol 36(5):528

    Article  Google Scholar 

  48. Ferwerda B et al (2009) Human dectin-1 deficiency and mucocutaneous fungal infections. N Engl J Med 361(18):1760–1767

    Article  CAS  Google Scholar 

  49. Shamriz O et al (2020) Chronic mucocutaneous candidiasis in early life: insights into immune mechanisms and novel targeted therapies. Front Immunol 11:593289

  50. Gavino C et al (2014) CARD9 deficiency and spontaneous central nervous system candidiasis: complete clinical remission with GM-CSF therapy. Clin Infect Dis 59(1):81–84

    Article  CAS  Google Scholar 

  51. Orth G (2006) Genetics of epidermodysplasia verruciformis: insights into host defense against papillomaviruses. Semin Immunol 18(6):362–374

    Article  CAS  Google Scholar 

  52. Crequer A et al (2013) EVER2 deficiency is associated with mild T-cell abnormalities. J Clin Immunol 33(1):14–21

    Article  CAS  Google Scholar 

  53. Akgul B et al (2007) A distinct variant of Epidermodysplasia verruciformis in a Turkish family lacking EVER1 and EVER2 mutations. J Dermatol Sci 46(3):214–216

    Article  Google Scholar 

  54. de Jong SJ et al (2018) Epidermodysplasia verruciformis: inborn errors of immunity to human beta-papillomaviruses. Front Microbiol 9:1222

    Article  Google Scholar 

  55. Ramoz N et al (2002) Mutations in two adjacent novel genes are associated with epidermodysplasia verruciformis. Nat Genet 32(4):579–581

    Article  CAS  Google Scholar 

  56. Lazarczyk M et al (2012) EVER proteins, key elements of the natural anti-human papillomavirus barrier, are regulated upon T-cell activation. PLoS One 7(6):e39995

  57. Crequer A et al (2012) Inherited MST1 deficiency underlies susceptibility to EV-HPV infections. PLoS One 7(8):e44010

  58. de Jong SJ et al (2018) The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to beta-papillomaviruses. J Exp Med 215(9):2289–2310

    Article  Google Scholar 

  59. Nehme NT et al (2012) MST1 mutations in autosomal recessive primary immunodeficiency characterized by defective naive T-cell survival. Blood 119(15):3458–3468

    Article  CAS  Google Scholar 

  60. Platt CD et al (2017) Combined immunodeficiency with EBV positive B cell lymphoma and epidermodysplasia verruciformis due to a novel homozygous mutation in RASGRP1. Clin Immunol 183:142–144

    Article  CAS  Google Scholar 

  61. Youssefian L et al (2019) Inherited Interleukin 2-Inducible T-Cell (ITK) Kinase deficiency in siblings with Epidermodysplasia Verruciformis and Hodgkin Lymphoma. Clin Infect Dis 68(11):1938–1941

    Article  CAS  Google Scholar 

  62. Lawrence T et al (2005) Autosomal-dominant primary immunodeficiencies. Curr Opin Hematol 12(1):22–30

    Article  CAS  Google Scholar 

  63. Bolze A et al (2013) Ribosomal protein SA haploinsufficiency in humans with isolated congenital asplenia. Science 340(6135):976–978

    Article  CAS  Google Scholar 

  64. Dinauer MC (2019) Inflammatory consequences of inherited disorders affecting neutrophil function. Blood 133(20):2130–2139

    Article  CAS  Google Scholar 

  65. Boztug K et al (2009) A syndrome with congenital neutropenia and mutations in G6PC3. N Engl J Med 360(1):32–43

    Article  CAS  Google Scholar 

  66. Skokowa J et al (2017) Severe congenital neutropenias. Nat Rev Dis Primers 3:17032

    Article  Google Scholar 

  67. Venugopal P et al (2020) Two monogenic disorders masquerading as one: severe congenital neutropenia with monocytosis and non-syndromic sensorineural hearing loss. BMC Med Genet 21(1):35

    Article  Google Scholar 

  68. Person RE et al (2003) Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2. Nat Genet 34(3):308–312

    Article  CAS  Google Scholar 

  69. Lyu B, Lyu W, Zhang X (2020) Kostmann syndrome with neurological abnormalities: a case report and literature review. Front Pediatr 8:586859

  70. Shah RK et al (2017) A novel homozygous VPS45 p.P468L mutation leading to severe congenital neutropenia with myelofibrosis. Pediatr Blood Cancer 64(9)

  71. Bellanne-Chantelot C et al (2018) Mutations in the SRP54 gene cause severe congenital neutropenia as well as Shwachman-Diamond-like syndrome. Blood 132(12):1318–1331

    Article  CAS  Google Scholar 

  72. Khandagale A et al (2021) Severe congenital neutropenia-associated JAGN1 mutations unleash a calpain-dependent cell death programme in myeloid cells. Br J Haematol 192(1):200–211

    Article  CAS  Google Scholar 

  73. Dong F et al (1995) Mutations in the gene for the granulocyte colony-stimulating-factor receptor in patients with acute myeloid leukemia preceded by severe congenital neutropenia. N Engl J Med 333(8):487–493

    Article  CAS  Google Scholar 

  74. Makaryan V et al (2014) TCIRG1-associated congenital neutropenia. Hum Mutat 35(7):824–827

    Article  CAS  Google Scholar 

  75. Dale DC et al (1993) A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia. Blood 81(10):2496–2502

    Article  CAS  Google Scholar 

  76. Fagerholm SC et al (2019) Beta2-Integrins and interacting proteins in Leukocyte trafficking, immune suppression, and immunodeficiency disease. Front Immunol 10:254

    Article  CAS  Google Scholar 

  77. Moutsopoulos NM et al (2017) Interleukin-12 and Interleukin-23 Blockade in Leukocyte Adhesion Deficiency Type 1. N Engl J Med 376(12):1141–1146

    Article  CAS  Google Scholar 

  78. Wolach B et al (2019) Leucocyte adhesion deficiency-A multicentre national experience. Eur J Clin Invest 49(2):e13047

  79. Gazit Y et al (2010) Leukocyte adhesion deficiency type II: long-term follow-up and review of the literature. J Clin Immunol 30(2):308–313

    Article  CAS  Google Scholar 

  80. Etzioni A (2010) Defects in the leukocyte adhesion cascade. Clin Rev Allergy Immunol 38(1):54–60

    Article  CAS  Google Scholar 

  81. Svensson L et al (2009) Leukocyte adhesion deficiency-III is caused by mutations in KINDLIN3 affecting integrin activation. Nat Med 15(3):306–312

    Article  CAS  Google Scholar 

  82. Essa MF et al (2020) Successful hematopoietic stem cell transplant in leukocyte adhesion deficiency type III presenting primarily as malignant infantile osteopetrosis. Clin Immunol 213:108365

  83. Heusinkveld LE et al (2019) WHIM Syndrome: from Pathogenesis Towards Personalized Medicine and Cure. J Clin Immunol 39(6):532–556

    Article  CAS  Google Scholar 

  84. Badolato R et al (2012) Tetralogy of fallot is an uncommon manifestation of warts, hypogammaglobulinemia, infections, and myelokathexis syndrome. J Pediatr 161(4):763–765

    Article  Google Scholar 

  85. McDermott DH et al (2011) The CXCR4 antagonist plerixafor corrects panleukopenia in patients with WHIM syndrome. Blood 118(18):4957–4962

    Article  CAS  Google Scholar 

  86. McDermott DH et al (2019) Plerixafor for the treatment of WHIM syndrome. N Engl J Med 380(2):163–170

    Article  CAS  Google Scholar 

  87. Dale DC et al (2020) Results of a phase 2 trial of an oral CXCR4 antagonist, mavorixafor, for treatment of WHIM syndrome. Blood 136(26):2994–3003

    Article  CAS  Google Scholar 

  88. Krivan G et al (2010) Successful umbilical cord blood stem cell transplantation in a child with WHIM syndrome. Eur J Haematol 84(3):274–275

    Article  CAS  Google Scholar 

  89. Moens L et al (2016) Successful hematopoietic stem cell transplantation for myelofibrosis in an adult with warts-hypogammaglobulinemia-immunodeficiency-myelokathexis syndrome. J Allergy Clin Immunol 138(5):1485–1489 e2

  90. Yu HH, Yang YH, Chiang BL (2020) Chronic granulomatous disease: a comprehensive review. Clin Rev Allergy Immunol

  91. Gennery AR (2021) Progress in treating chronic granulomatous disease. Br J Haematol 192(2):251–264

    Article  CAS  Google Scholar 

  92. Marciano BE et al (2015) Common severe infections in chronic granulomatous disease. Clin Infect Dis 60(8):1176–1183

    Article  CAS  Google Scholar 

  93. van de Geer A et al (2018) Inherited p40phox deficiency differs from classic chronic granulomatous disease. J Clin Invest 128(9):3957–3975

    Article  Google Scholar 

  94. Ambruso DR et al (2000) Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation. Proc Natl Acad Sci USA 97(9):4654–4659

    Article  CAS  Google Scholar 

  95. Marciano BE et al (2018) X-linked carriers of chronic granulomatous disease: Illness, lyonization, and stability. J Allergy Clin Immunol 141(1):365–371

    Article  CAS  Google Scholar 

  96. Blancas-Galicia L et al (2020) Genetic, immunological, and clinical features of the first Mexican cohort of patients with chronic granulomatous disease. J Clin Immunol 40(3):475–493

    Article  CAS  Google Scholar 

  97. Seidel MG et al (2019) The European Society for Immunodeficiencies (ESID) registry working definitions for the clinical diagnosis of inborn errors of immunity. J Allergy Clin Immunol Pract 7(6):1763–1770

    Article  Google Scholar 

  98. Kuhns DB et al (2010) Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med 363(27):2600–2610

    Article  CAS  Google Scholar 

  99. The International Chronic Granulomatous Disease Cooperative Study Group (1991) A controlled trial of interferon gamma to prevent infection in chronic granulomatous disease. N Engl J Med 324(8):509–516

  100. Martire B et al (2008) Clinical features, long-term follow-up and outcome of a large cohort of patients with chronic granulomatous disease: an Italian multicenter study. Clin Immunol 126(2):155–164

    Article  CAS  Google Scholar 

  101. Dedieu C et al (2020) Outcome of chronic granulomatous disease - conventional treatment vs stem cell transplantation. Pediatr Allergy Immunol

  102. Chiesa R et al (2020) Hematopoietic cell transplantation in chronic granulomatous disease: a study of 712 children and adults. Blood 136(10):1201–1211

    Article  Google Scholar 

  103. Kohn DB et al (2020) Lentiviral gene therapy for X-linked chronic granulomatous disease. Nat Med 26(2):200–206

    Article  CAS  Google Scholar 

  104. Orange JS (2013) Natural killer cell deficiency. J Allergy Clin Immunol 132(3):515–525

    Article  CAS  Google Scholar 

  105. Vargas-Hernandez A, Forbes LR (2019) The impact of immunodeficiency on NK cell maturation and function. Curr Allergy Asthma Rep 19(1):2

    Article  Google Scholar 

  106. Spinner MA et al (2014) GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity. Blood 123(6):809–821

    Article  CAS  Google Scholar 

  107. Bogaert DJ et al (2020) GATA2 deficiency and haematopoietic stem cell transplantation: challenges for the clinical practitioner. Br J Haematol 188(5):768–773

    Article  Google Scholar 

  108. Hughes CR et al (2012) MCM4 mutation causes adrenal failure, short stature, and natural killer cell deficiency in humans. J Clin Invest 122(3):814–820

    Article  CAS  Google Scholar 

  109. Gineau L et al (2012) Partial MCM4 deficiency in patients with growth retardation, adrenal insufficiency, and natural killer cell deficiency. J Clin Invest 122(3):821–832

    Article  CAS  Google Scholar 

  110. Mace EM et al (2017) Biallelic mutations in IRF8 impair human NK cell maturation and function. J Clin Invest 127(1):306–320

    Article  Google Scholar 

  111. Cottineau J et al (2017) Inherited GINS1 deficiency underlies growth retardation along with neutropenia and NK cell deficiency. J Clin Invest 127(5):1991–2006

    Article  Google Scholar 

  112. Grier JT et al (2012) Human immunodeficiency-causing mutation defines CD16 in spontaneous NK cell cytotoxicity. J Clin Invest 122(10):3769–3780

    Article  CAS  Google Scholar 

  113. Diana J, Lehuen A (2009) NKT cells: friend or foe during viral infections? Eur J Immunol 39(12):3283–3291

    Article  CAS  Google Scholar 

  114. Grumach AS, Kirschfink M (2014) Are complement deficiencies really rare? Overview on prevalence, clinical importance and modern diagnostic approach. Mol Immunol 61(2):110–117

    Article  CAS  Google Scholar 

  115. Kirschfink M, Mollnes TE (2003) Modern complement analysis. Clin Diagn Lab Immunol 10(6):982–989

    CAS  Google Scholar 

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Akar-Ghibril, N. Defects of the Innate Immune System and Related Immune Deficiencies. Clinic Rev Allerg Immunol 63, 36–54 (2022). https://doi.org/10.1007/s12016-021-08885-y

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