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Chronic Granulomatous Disease

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Primary and Secondary Immunodeficiency

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Abstract

Chronic granulomatous disease (CGD) is an inherited primary immunodeficiency due to mutations in any of the critical subunits of the phagocyte NADPH oxidase complex, resulting in impaired oxidase activity of neutrophils, monocytes, and tissue macrophages. It is characterized by increased susceptibility to recurrent and severe infections with a narrow pathognomonic spectrum of bacteria and fungi, granuloma formation, and inflammatory disease, primarily of the gastrointestinal tract, lungs, and liver. Inflammatory disease in CGD is difficult to predict and often refractory to therapy. Patients with CGD also have increased incidence of autoimmune disease, including lupus-like symptoms, sarcoidosis, IgA nephropathy, rheumatoid arthritis, and other autoimmune manifestations. With increasing awareness of disease, widespread use of antimicrobial prophylaxis, and advancements in hematopoietic stem cell transplantation (HSCT), outcomes have improved dramatically and many patients now live well into adulthood. HSCT is the only widely available definitive treatment for CGD with the potential for resolution of both infectious and inflammatory complications. Overall survival rates are now consistently near or >90% for pediatric patients less than 14 years regardless of donor source, and survival rates are improving for adolescents and young adults, including those with severe infection and/or uncontrolled inflammatory disease at time of transplantation. Early results from gene therapy trials have also demonstrated resolution of the CGD phenotype, although long-term outcomes with gene therapy are unknown.

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References

  1. Janeway CA, Craig J, Davison M, et al. Hypergammaglobulinemia associated with severe, recurrent, and chronic non-specific infection. Am J Dis Child. 1954;88:388–92.

    Google Scholar 

  2. Bridges RA, Berendes H, Good RA. A fatal granulomatous disease of childhood; the clinical, pathological, and laboratory features of a new syndrome. AMA J Dis Child. 1959;97(4):387–408.

    Article  CAS  PubMed  Google Scholar 

  3. Reeves EP, Lu H, Jacobs HL, et al. Killing activity of neutrophils is mediated through activation of proteases by K+ flux. Nature. 2002;416(6878):291–7.

    Article  CAS  PubMed  Google Scholar 

  4. Fuchs TA, Abed U, Goosmann C, et al. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol. 2007;176(2):231–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Winkelstein JA, Marino MC, Johnston RB, et al. Chronic granulomatous disease: report on a national registry of 368 patients. Medicine. 2000;79(3):155–69.

    Article  CAS  PubMed  Google Scholar 

  6. Jones LB, McGrogan P, Flood TJ, et al. Special article: chronic granulomatous disease in the United Kingdom and Ireland: a comprehensive national patient-based registry. Clin Exp Immunol. 2008;152(2):211–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Martire B, Rondelli R, Soresina A, et al. Clinical features, long-term follow-up and outcome of a large cohort of patients with chronic granulomatous disease: an Italian multicenter study. Clin Immunol. 2008;126(2):155–64.

    Article  CAS  PubMed  Google Scholar 

  8. Åhlin A, de Boer M, Roos D, et al. Prevalence, genetics and clinical presentation of chronic granulomatous disease in Sweden. Acta Paediatr. 1995;84(2):1386–94.

    Article  PubMed  Google Scholar 

  9. Raptaki M, Varela I, Spanou K, et al. Chronic granulomatous disease: a 25-year patient registry based on a multistep diagnostic procedure, from the referral center for primary immunodeficiencies in Greece. J Clin Immunol. 2013;33(8):1302–9.

    Article  PubMed  Google Scholar 

  10. Hasui M, Hayakawa H, Kanegasaki S, et al. Chronic granulomatous disease in Japan: incidence and natural history. Pediatr Int. 1999;41(5):589–93.

    Article  CAS  PubMed  Google Scholar 

  11. Wolach B, Gavrieli R, de Boer M, et al. Chronic granulomatous disease: clinical, functional, molecular, and genetic studies. The Israeli experience with 84 patients. Am J Hematol. 2017;92(1):28–36.

    Article  CAS  PubMed  Google Scholar 

  12. van den Berg J, van Koppen E, Ahlin A, et al. Chronic granulomatous disease: the European experience. PLoS ONE. 2009;4(4):e5234.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Roos D, Kuhns DB, Maddalena A, et al. Hematologically important mutations: the autosomal recessive forms of chronic granulomatous disease (second update). Blood Cell Mol Dis. 2010;44(4):291–9.

    Article  CAS  Google Scholar 

  14. Kuhns DB, Alvord WG, Heller T, et al. Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med. 2010;363(27):2600–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Matute JD, Arias AA, Wright NAM, et al. A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40 phox and selective defects in neutrophil NADPH oxidase activity. Blood. 2009;114(5):3309–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. van de Geer A, Nieto-Patlán A, Kuhns DB, et al. Inherited p40 phox deficiency differs from classic chronic granulomatous disease. J Clin Invest. 2018;128(9):3957–75.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Thomas DC, Charbonnier LM, Schejtman A, et al. EROS/CYBC1 mutations: decreased NADPH oxidase function and chronic granulomatous disease. J Allergy Clin Immunol. 2019;143(2):782–5.

    Article  CAS  PubMed  Google Scholar 

  18. Arnadottir GA, Norddahl GL, Gudmundsdottir S, et al. A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease. Nat Commun. 2018;9(1):4447.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Marciano BE, Spalding C, Fitzgerald A, et al. Common severe infections in chronic granulomatous disease. Clin Infect Dis. 2015;60(8):1176–83.

    Article  CAS  PubMed  Google Scholar 

  20. Bortoletto P, Lyman K, Camacho A, et al. Chronic granulomatous disease: a large, single-center US experience. Pediatr Infect Dis J. 2015;34(10):1110–4.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Wolach B, Gavrieli R, de Boer M, et al. Chronic granulomatous disease in Israel: clinical, functional and molecular studies of 38 patients. Clin Immunol. 2008;129(1):103–14.

    Article  CAS  PubMed  Google Scholar 

  22. Baba LA, Ailal F, el Hafidi N, et al. Chronic granulomatous disease in Morocco: genetic, immunological, and clinical features of 12 patients from 10 kindreds. J Clin Immunol. 2014;34(4):452–8.

    PubMed  Google Scholar 

  23. de Oliveira-Junior EB, Zurro NB, Prando C, et al. Clinical and genotypic spectrum of chronic granulomatous disease in 71 Latin American patients: first report from the LASID registry. Pediatr Blood Cancer. 2015;62(12):2102–7.

    Article  CAS  Google Scholar 

  24. Fattahi F, Badalzadeh M, Sedighipour L, et al. Inheritance pattern and clinical aspects of 93 Iranian patients with chronic granulomatous disease. J Clin Immunol. 2011;31(5):792–801.

    Article  PubMed  Google Scholar 

  25. Zhou Q, Hui X, Ying W, et al. A cohort of 169 chronic granulomatous disease patients exposed to BCG vaccination: a retrospective study from a single center in Shanghai, China (2004–2017). J Clin Immunol. 2018;38(3):260–72.

    Article  CAS  PubMed  Google Scholar 

  26. Lee PPW, Chan KW, Jiang L, et al. Susceptibility to mycobacterial infections in children with x-linked chronic granulomatous disease: a review of 17 patients living in a region endemic for tuberculosis. Pediatr Infect Dis J. 2008;27(3):224–30.

    Article  PubMed  Google Scholar 

  27. Conti F, Lugo-Reyes SO, Blancas Galicia L, et al. Mycobacterial disease in patients with chronic granulomatous disease: a retrospective analysis of 71 cases. J Allergy Clin Immunol. 2016;138(1):241–8.

    Article  PubMed  Google Scholar 

  28. Sirinavin S, Techasaensiri C, Benjaponpitak S, Pornkul R, Vorachit M. Invasive Chromobacterium violaceum infection in children: case report and review. Pediatr Infect Dis J. 2005;24(6):559–61.

    Article  PubMed  Google Scholar 

  29. Meher-Homji Z, Mangalore RP, D R Johnson P, Y L Chua K. Chromobacterium violaceum infection in chronic granulomatous disease: a case report and review of the literature. JMM Case Rep. 2017;4(1):e005084.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Mailman TL, Schmidt MH. Francisella philomiragia adenitis and pulmonary nodules in a child with chronic granulomatous disease. Can J Infect Dis Med Microbiol. 2005;16(4):245–8.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Greenberg DE, Shoffner AR, Zelazny AM, et al. Recurrent granulibacter bethesdensis infections and chronic granulomatous disease. Emerg Infect Dis. 2010;16(9):1341–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Dotis J, Roilides E. Osteomyelitis due to Aspergillus species in chronic granulomatous disease: an update of the literature. Mycoses. 2011;54(6):e686–96.

    Article  PubMed  Google Scholar 

  33. Falcone EL, Holland SM. Invasive fungal infection in chronic granulomatous disease: insights into pathogenesis and management. Curr Opin Infect Dis. 2012;25(6):658–69.

    Article  PubMed  Google Scholar 

  34. Beauté J, Obenga G, le Mignot L, et al. Epidemiology and outcome of invasive fungal diseases in patients with chronic granulomatous disease: a multicenter study in France. Pediatr Infect Dis J. 2011;30(1):57–62.

    Article  PubMed  Google Scholar 

  35. Blumental S, Mouy R, Mahlaoui N, et al. Invasive mold infections in chronic granulomatous disease: a 25-year retrospective survey. Clin Infect Dis. 2011;53(12):e159–69.

    Article  PubMed  Google Scholar 

  36. Vinh DC, Shea YR, Jones PA, et al. Chronic invasive aspergillosis caused by Aspergillus viridinutans. Emerg Infect Dis. 2009;15(8):1292–4.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Sugui JA, Peterson SW, Clark LP, et al. Aspergillus tanneri sp. nov., a new pathogen that causes invasive disease refractory to antifungal therapy. J Clin Microbiol. 2012;50(10):3309–17.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Kaltenis P, Mudänienè V, Maknavičius S, Šeinin D. Renal amyloidosis in a child with chronic granulomatous disease and invasive aspergillosis. Pediatr Nephrol. 2008;23(5):831–4.

    Article  PubMed  Google Scholar 

  39. Mortaz E, Sarhifynia S, Marjani M, et al. An adult autosomal recessive chronic granulomatous disease patient with pulmonary Aspergillus terreus infection. BMC Infect Dis. 2018;18(1):552.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Dotis J, Pana ZD, Roilides E. Non-Aspergillus fungal infections in chronic granulomatous disease. Mycoses. 2013;56(4):449–62.

    Article  PubMed  Google Scholar 

  41. Silliman CC, Lawellin DW, Lohr JA, Rodgers BM, Donowitz LG. Paecilomyces lilacinus infection in a child with chronic granulomatous disease. J Infect. 1992;24(2):191–5.

    Article  CAS  PubMed  Google Scholar 

  42. Wang SM, Shieh CC, Liu CC. Successful treatment of Paecilomyces variotii splenic abscesses: a rare complication in a previously unrecognized chronic granulomatous disease child. Diagn Microbiol Infect Dis. 2005;53(2):149–52.

    Article  PubMed  Google Scholar 

  43. Ramesh M, Resnick E, Hui Y, et al. Phellinus tropicalis abscesses in a patient with chronic granulomatous disease. J Clin Immunol. 2014;34(2):130–3.

    Article  PubMed  Google Scholar 

  44. Haidar G, Zerbe CS, Cheng M, et al. Phellinus species: an emerging cause of refractory fungal infections in patients with X-linked chronic granulomatous disease. Mycoses. 2017;60(3):155–60.

    Article  CAS  PubMed  Google Scholar 

  45. de Ravin SS, Challipalli M, Anderson V, et al. Geosmithia argillacea: an emerging cause of invasive mycosis in human chronic granulomatous disease. Clin Infect Dis. 2011;52(6):e136–43.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Vinh DC, Shea YR, Sugui JA, et al. Invasive Aspergillosis due to Neosartorya udagawae. Clin Infect Dis. 2009;49(1):102–11.

    Article  PubMed  Google Scholar 

  47. Vinh DC, Freeman AF, Shea YR, et al. Mucormycosis in chronic granulomatous disease: association with iatrogenic immunosuppression. J Allergy Clin Immunol. 2009;123(6):1411–3.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Siler U, Romao S, Tejera E, et al. Severe glucose-6-phosphate dehydrogenase deficiency leads to susceptibility to infection and absent NETosis. J Allergy Clin Immunol. 2017;139(1):212–9.

    Article  CAS  PubMed  Google Scholar 

  49. Mauch L, Lun A, O’Gorman MRG, et al. Chronic granulomatous disease (CGD) and complete myeloperoxidase deficiency both yield strongly reduced dihydrorhodamine 123 test signals but can be easily discerned in routine testing for CGD. Clin Chem. 2007;53(5):890–6.

    Article  CAS  PubMed  Google Scholar 

  50. Ferguson PJ, Lokuta MA, El-Shanti HI, et al. Neutrophil dysfunction in a family with a SAPHO syndrome-like phenotype. Arthritis Rheum. 2008;58(10):3264–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Banerjee R, Anguita J, Roos D, Fikrig E. Cutting edge: infection by the agent of human granulocytic ehrlichiosis prevents the respiratory burst by down-regulating gp91phox. J Immunol. 2000;164(8):3946–9.

    Article  CAS  PubMed  Google Scholar 

  52. Kuhns DB, Wu X, Hsu AP, et al. Characterization of patients and carriers of p47phox chronic granulomatous disease by flow cytometric analysis of p47phox expression and droplet digital PCR analysis of NCF1. J Clin Immunol. 2018;38(3):349.

    Google Scholar 

  53. Kuhns DB, Hsu AP, Sun D, et al. NCF1 (p47 phox)-deficient chronic granulomatous disease: comprehensive genetic and flow cytometric analysis. Blood Adv. 2019;3(2):136–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Gallin JI, Buescher ES, Seligmann BE, et al. NIH conference. Recent advances in chronic granulomatous disease. Ann Intern Med. 1983;99(5):657–74.

    Article  CAS  PubMed  Google Scholar 

  55. Forrest CB, Forehand JR, Axtell RA, Roberts RL, Johnston RB. Clinical features and current management of chronic granulomatous disease. Hematol Oncol Clin N Am. 1988;2(2):253–66.

    Article  CAS  Google Scholar 

  56. Weening RS, Kabel P, Pijman P, Roos D. Continuous therapy with sulfamethoxazole-trimethoprim in patients with chronic granulomatous disease. J Pediatr. 1983;103(1):127–30.

    Article  CAS  PubMed  Google Scholar 

  57. Mouy R. Chronic septic granulomatosis. Clinical and therapeutic aspects. Ann Pediatr. 1989;36(6):374–8.

    CAS  Google Scholar 

  58. Margolis DM, Melnick DA, Alling DW, Gallin JI. Trimethoprim-sulfamethoxazole prophylaxis in the management of chronic granulomatous disease. J Infect Dis. 1990;162(3):723–6.

    Article  CAS  PubMed  Google Scholar 

  59. Gallin JI, Alling DW, Malech HL, et al. Itraconazole to prevent fungal infections in chronic granulomatous disease. N Engl J Med. 2003;348(24):2416–22.

    Article  CAS  PubMed  Google Scholar 

  60. Segal BH, Barnhart LA, Anderson VL, et al. Posaconazole as salvage therapy in patients with chronic granulomatous disease and invasive filamentous fungal infection. Clin Infect Dis. 2005;40(11):1684–8.

    Article  CAS  PubMed  Google Scholar 

  61. Gallin JI, Malech HL, Weening RS, et al. A controlled trial of interferon gamma to prevent infection in chronic granulomatous disease: the international chronic granulomatous disease cooperative study group. N Engl J Med. 1991;324(8):509–16.

    Article  Google Scholar 

  62. Marciano BE, Wesley R, de Carlo ES, et al. Long-term interferon-therapy for patients with chronic granulomatous disease. Clin Infect Dis. 2004;39(5):692–9.

    Article  CAS  PubMed  Google Scholar 

  63. Marciano BE, Allen ES, Conry-Cantilena C, et al. Granulocyte transfusions in patients with chronic granulomatous disease and refractory infections: the NIH experience. J Allergy Clin Immunol. 2017;140(2):622–5.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Stroncek DF, Leonard K, Eiber G, et al. Alloimmunization after granulocyte transfusions. Transfusion. 1996;75(3):744–55.

    Google Scholar 

  65. Heim KF, Fleisher TA, Stroncek DF, et al. The relationship between alloimmunization and posttransfusion granulocyte survival: experience in a chronic granulomatous disease cohort. Transfusion. 2011;51(6):1154–62.

    Article  CAS  PubMed  Google Scholar 

  66. Parta M, Kelly C, Kwatemaa N, et al. Allogeneic reduced-intensity hematopoietic stem cell transplantation for chronic granulomatous disease: a single-center prospective trial. J Clin Immunol. 2017;37(6):548–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Yamazaki-Nakashimada MA, Stiehm ER, Pietropaolo-Cienfuegos D, Hernandez-Bautista V, Espinosa-Rosales F. Corticosteroid therapy for refractory infections in chronic granulomatous disease: case reports and review of the literature. Ann Allergy Asthma Immunol. 2006;97(2):257–61.

    Article  CAS  PubMed  Google Scholar 

  68. Freeman AF, Marciano BE, Anderson VL, et al. Corticosteroids in the treatment of severe nocardia pneumonia in chronic granulomatous disease. Pediatr Infect Dis J. 2011;30(9):806–8.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Leiding JW, Freeman AF, Marciano BE, et al. Corticosteroid therapy for liver abscess in chronic granulomatous disease. Clin Infect Dis. 2012;54(5):694–700.

    Article  CAS  PubMed  Google Scholar 

  70. Straughan DM, McLoughlin KC, Mullinax JE, et al. The changing paradigm of management of liver abscesses in chronic granulomatous disease. Clin Infect Dis. 2018;66(9):1427–34.

    Article  CAS  PubMed  Google Scholar 

  71. Magnani A, Brosselin P, Beauté J, et al. Inflammatory manifestations in a single-center cohort of patients with chronic granulomatous disease. J Allergy Clin Immunol. 2014;134(3):655–62.

    Article  PubMed  Google Scholar 

  72. Dunogué B, Pilmis B, Mahlaoui N, et al. Chronic granulomatous disease in patients reaching adulthood: a nationwide study in France. Clin Infect Dis. 2017;64(6):767–75.

    Article  PubMed  Google Scholar 

  73. Marciano BE, Rosenzweig SD, Kleiner DE, et al. Gastrointestinal involvement in chronic granulomatous disease. Pediatrics. 2004;114(2):462–8.

    Article  PubMed  Google Scholar 

  74. Alimchandani M, Lai JP, Aung PP, et al. Gastrointestinal histopathology in chronic granulomatous disease a study of 87 patients. Am J Surg Pathol. 2013;37(9):1365–72.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Johnson FE, Humbert JR, Kuzela DC, Todd JK, Lilly JR. Gastric outlet obstruction due to X-linked chronic granulomatous disease. Surgery. 1975;78(2):217–23.

    CAS  PubMed  Google Scholar 

  76. Salvator H, Mahlaoui N, Catherinot E, et al. Pulmonary manifestations in adult patients with chronic granulomatous disease. Eur Respir J. 2015;45(6):1613–23.

    Article  PubMed  Google Scholar 

  77. Mahdaviani SA, Mohajerani SA, Rezaei N, et al. Pulmonary manifestations of chronic granulomatous disease. Expert Rev Clin Immunol. 2013;9(2):153–60.

    Article  CAS  PubMed  Google Scholar 

  78. Hussain N, Feld JJ, Kleiner DE, et al. Hepatic abnormalities in patients with chronic granulomatous disease. Hepatology. 2007;45(3):675–83.

    Article  PubMed  Google Scholar 

  79. Feld JJ, Hussain N, Wright EC, et al. Hepatic involvement and portal hypertension predict mortality in chronic granulomatous disease. Gastroenterology. 2008;134(7):1917–26.

    Article  PubMed  Google Scholar 

  80. Walther MM, Malech H, Berman A, et al. The urological manifestations of chronic granulomatous disease. J Urol. 1992;147(5):1314–8.

    Article  CAS  PubMed  Google Scholar 

  81. Barese CN, Podestá M, Litvak E, Villa M, Rivas EM. Recurrent eosinophilic cystitis in a child with chronic granulomatous disease. J Pediatr Hematol Oncol. 2004;26(3):209–12.

    Article  PubMed  Google Scholar 

  82. Claps A, della Corte M, Gerocarni Nappo S, et al. How should eosinophilic cystitis be treated in patients with chronic granulomatous disease? Pediatr Nephrol. 2014;29(11):2229–33.

    Article  PubMed  Google Scholar 

  83. Eckert JW, Abramson SL, Starke J, Brandt ML. The surgical implications of chronic granulomatous disease. Am J Surg. 1995;169(3):320–3.

    Article  CAS  PubMed  Google Scholar 

  84. Feingold PL, Quadri HS, Steinberg SM, et al. Thoracic surgery in chronic granulomatous disease: a 25-year single-institution experience. J Clin Immunol. 2016;36(7):677–83.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Akagi K, Kawai T, Watanabe N, et al. A case of macrophage activation syndrome developing in a patient with chronic granulomatous disease-associated colitis. J Pediatr Hematol Oncol. 2014;36(3):e169–72.

    Article  PubMed  Google Scholar 

  86. Valentine G, Thomas TA, Nguyen T, Lai YC. Chronic granulomatous disease presenting as hemophagocytic lymphohistiocytosis: a case report. Pediatrics. 2014;134(6):e1727–30.

    Article  PubMed  Google Scholar 

  87. Parekh C, Hofstra T, Church JA, Coates TD. Hemophagocytic lymphohistiocytosis in children with chronic granulomatous disease. Pediatr Blood Cancer. 2011;56(3):460–2.

    Article  PubMed  Google Scholar 

  88. Bode SFN, Ammann S, Al-Herz W, et al. The syndrome of hemophagocytic lymphohistiocytosis in primary immunodeficiencies: implications for differential diagnosis and pathogenesis. Haematologica. 2015;100(7):978–88.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Siddiqui S, Anderson VL, Hilligoss DM, et al. Fulminant mulch pneumonitis: an emergency presentation of chronic granulomatous disease. Clin Infect Dis. 2007;45(6):673–81.

    Article  CAS  PubMed  Google Scholar 

  90. Ameratunga R, Woon ST, Vyas J, Roberts S. Fulminant mulch pneumonitis in undiagnosed chronic granulomatous disease: a medical emergency. Clin Pediatr. 2010;49(12):1143–6.

    Article  Google Scholar 

  91. Maaloul I, Ben Ameur S, Chabchoub I, et al. Fulminant mulch pneumonitis in a previously healthy child. Arch Pediatr. 2018;25(8):495–6.

    Article  CAS  PubMed  Google Scholar 

  92. Battersby AC, Braggins H, Pearce MS, et al. Inflammatory and autoimmune manifestations in X-linked carriers of chronic granulomatous disease in the United Kingdom. J Allergy Clin Immunol. 2017;140(2):628–30.

    Article  PubMed  Google Scholar 

  93. Marciano BE, Zerbe CS, Falcone EL, et al. X-linked carriers of chronic granulomatous disease: illness, lyonization, and stability. J Allergy Clin Immunol. 2018;141(1):365–71.

    Article  CAS  PubMed  Google Scholar 

  94. Battersby A, Braggins H, Pearce M, et al. Health-related quality of life and emotional health in X-linked carriers of chronic granulomatous disease in the United Kingdom. J Clin Immunol. 2019;39(2):195–9.

    Article  PubMed  PubMed Central  Google Scholar 

  95. de Luca A, Smeekens SP, Casagrande A, et al. IL-1 receptor blockade restores autophagy and reduces inflammation in chronic granulomatous disease in mice and in humans. Proc Natl Acad Sci U S A. 2014;111(9):3526–31.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Hahn KJ, Ho N, Yockey L, et al. Treatment with Anakinra, a recombinant IL-1 receptor antagonist, unlikely to induce lasting remission in patients with CGD colitis. Am J Gastroenterol. 2015;110(6):938–9.

    Article  CAS  PubMed  Google Scholar 

  97. Butte MJ, Park KT, Lewis DB. Treatment of CGD-associated colitis with the IL-23 blocker ustekinumab. J Clin Immunol. 2016;36(7):619–20.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Campbell N, Chapdelaine H. Treatment of chronic granulomatous disease–associated fistulising colitis with vedolizumab. J Allergy Clin Immunol Pract. 2017;5(6):1748–9.

    Article  PubMed  Google Scholar 

  99. Horwitz ME. Stem-cell transplantation for inherited immunodeficiency disorders. Pediatr Clin North Am. 2000;47(6):1371–87. https://doi.org/10.1016/s0031-3955(05)70276-5. Pediatr Clin North Am. 2000. PMID: 11131001.

  100. Horwitz ME, Barrett AJ, Brown MR, et al. Treatment of chronic granulomatous disease with nonmyeloablative conditioning and a T-cell-depleted hematopoietic allograft. N Engl J Med. 2001;344(12):881–8.

    Article  CAS  PubMed  Google Scholar 

  101. Seger RA, Gungor T, Belohradsky BH, et al. Treatment of chronic granulomatous disease with myeloablative conditioning and an unmodified hemopoietic allograft: a survey of the European experience, 1985–2000. Blood. 2002;100(13):4344–50.

    Article  CAS  PubMed  Google Scholar 

  102. Schuetz C, Hoenig M, Gatz S, et al. Hematopoietic stem cell transplantation from matched unrelated donors in chronic granulomatous disease. Immunol Res. 2009;44(1–3):35–41.

    Article  CAS  PubMed  Google Scholar 

  103. Soncini E, Slatter MA, Jones LBKR, et al. Unrelated donor and HLA-identical sibling haematopoietic stem cell transplantation cure chronic granulomatous disease with good long-term outcome and growth. Br J Haematol. 2009;145(1):73–83.

    Article  CAS  PubMed  Google Scholar 

  104. Goździk J, Pituch-Noworolska A, Skoczeń S, et al. Allogeneic haematopoietic stem cell transplantation as therapy for chronic granulomatous disease-single centre experience. J Clin Immunol. 2011;31(3):322–7.

    Article  Google Scholar 

  105. Martinez CA, Shah S, Shearer WT, et al. Excellent survival after sibling or unrelated donor stem cell transplantation for chronic granulomatous disease. J Allergy Clin Immunol. 2012;129(1):176–83.

    Article  PubMed  Google Scholar 

  106. Tewari P, Martin PL, Mendizabal A, et al. Myeloablative transplantation using either cord blood or bone marrow leads to immune recovery, high long-term donor chimerism and excellent survival in chronic granulomatous disease. Biol Blood Marrow Transplant. 2012;18(9):1368–77.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Morillo-Gutierrez B, Beier R, Rao K, et al. Treosulfan-based conditioning for allogeneic HSCT in children with chronic granulomatous disease: a multicenter experience. Blood. 2016;128(21):2585.

    Google Scholar 

  108. Mehta B, Mahadeo K, Kapoor N, Abdel-Azim H. Low-dose total-body irradiation and alemtuzumab-based reduced-intensity conditioning regimen results in durable engraftment and correction of clinical disease among children with chronic granulomatous disease. Pediatr Transplant. 2015;19(4):408–12.

    Article  CAS  PubMed  Google Scholar 

  109. Lum SH, Flood T, Hambleton S, et al. Two decades of excellent transplant survival for chronic granulomatous disease: a supraregional immunology transplant center report. Blood. 2019;133(23):2547–9.

    Article  CAS  Google Scholar 

  110. Cole T, Pearce MS, Cant AJ, et al. Clinical outcome in children with chronic granulomatous disease managed conservatively or with hematopoietic stem cell transplantation. J Allergy Clin Immunol. 2013;132(5):1150–5.

    Article  PubMed  Google Scholar 

  111. Cole T, McKendrick F, Titman P, et al. Health related quality of life and emotional health in children with chronic granulomatous disease: a comparison of those managed conservatively with those that have undergone haematopoietic stem cell transplant. J Clin Immunol. 2013;33(1):8–13.

    Article  CAS  PubMed  Google Scholar 

  112. Yonkof JR, Gupta A, Fu P, Garabedian E, Dalal J. Role of allogeneic hematopoietic stem cell transplant for chronic granulomatous disease (CGD): a report of the United States Immunodeficiency Network. J Clin Immunol. 2019;39:448–58.

    Article  CAS  PubMed  Google Scholar 

  113. Güngör T, Teira P, Slatter M, et al. Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study. Lancet. 2014;383(9915):436–48.

    Article  PubMed  CAS  Google Scholar 

  114. Khandelwal P, Bleesing JJ, Davies SM, et al. A Single-Center Experience Comparing Alemtuzumab, Fludarabine, and Melphalan Reduced-Intensity Conditioning with Myeloablative Busulfan, Cyclophosphamide, and Antithymocyte Globulin for Chronic Granulomatous Disease. Biol Blood Marrow Transplant. 2016;22(11):2011–8. https://doi.org/10.1016/j.bbmt.2016.08.013. Epub 2016. Biol Blood Marrow Transplant. 2016. PMID: 27543157.

  115. Fox TA, Chakraverty R, Burns S, et al. Successful outcome following allogeneic hematopoietic stem cell transplantation in adults with primary immunodeficiency. Blood. 2018;131(8):917–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Parta M, Kelly C, Kwatemaa N, et al. Allogeneic Reduced-Intensity Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease: a Single-Center Prospective Trial. J Clin Immunol. 2017;37(6):548–58. https://doi.org/10.1007/s10875-017-0422-6. Epub 2017 Jul 28. J Clin Immunol. 2017. PMID: 28752258.

  117. Arnold DE, Sullivan KE, Jyonouchi S, et al. Immune reconstitution in six adolescents with chronic granulomatous disease following hematopoietic stem cell transplant. J Allergy Clin Immunol Pract. 2017;7(3):1052–4.

    Article  Google Scholar 

  118. Lum SH, Flood T, Hambleton S, et al. Two decades of excellent transplant survival for chronic granulomatous disease: a supraregional immunology transplant center report. Blood. 2019;133(23):2546–9. https://doi.org/10.1182/blood.2019000021. Epub 2019 Apr 5. Blood. 2019. PMID: 30952673.

  119. Oshrine B, Morsheimer M, Heimall J, Bunin N. Reduced-intensity conditioning for hematopoietic cell transplantation of chronic granulomatous disease. Pediatr Blood Cancer. 2015;62(2):359–61.

    Article  PubMed  Google Scholar 

  120. Marsh RA, Leiding JW, Logan BR, et al. Chronic granulomatous disease-associated IBD resolves and does not adversely impact survival following allogeneic HCT. J Clin Immunol. 2019;39(7):653–67.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Malech HL, Maples PB, Whiting-Theobald N, et al. Prolonged production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulomatous disease. Proc Natl Acad Sci U S A. 1997;94(22):12133–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Ott MG, Schmidt M, Schwarzwaelder K, et al. Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nat Med. 2006;12(4):401–9.

    Article  CAS  PubMed  Google Scholar 

  123. Stein S, Ott MG, Schultze-Strasser S, et al. Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease. Nat Med. 2010;16(2):198–204.

    Article  CAS  PubMed  Google Scholar 

  124. Bianchi M, Hakkim A, Brinkmann V, et al. Restoration of NET formation by gene therapy in CGD controls aspergillosis. Blood. 2009;114(13):2619–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Siler U, Paruzynski A, Holtgreve-Grez H, et al. Successful combination of sequential gene therapy and rescue allo-HSCT in two children with X-CGD – importance of timing. Curr Gene Ther. 2015;15(4):416–27.

    Article  CAS  PubMed  Google Scholar 

  126. Kang HJ, Bartholomae CC, Paruzynski A, et al. Retroviral gene therapy for X-linked chronic granulomatous disease: results from phase I/II trial. Mol Ther. 2011;19(11):2092–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Malech HL, Booth C, Kang EM, et al. Lentiviral vector gene therapy for X-linked chronic granulomatous disease corrects neutrophil function. J Clin Immunol. 2019;39(Suppl 1):S45.

    Google Scholar 

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  1. Immune Deficiency – Cellular Therapy Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Danielle E. Arnold & Jennifer R. Heimall

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  1. Danielle E. Arnold
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  2. Jennifer R. Heimall
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    Jonathan A. Bernstein

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Arnold, D.E., Heimall, J.R. (2021). Chronic Granulomatous Disease. In: Bernstein, J.A. (eds) Primary and Secondary Immunodeficiency. Springer, Cham. https://doi.org/10.1007/978-3-030-57157-3_17

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