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Dock8 Deficiency: Clinical and Immunological Phenotype and Treatment Options - a Review of 136 Patients Publisher Pubmed



Aydin SE1 ; Kilic SS2 ; Aytekin C3 ; Kumar A4 ; Porras O5 ; Kainulainen L6 ; Kostyuchenko L7 ; Genel F8 ; Kutukculer N9 ; Karaca N9 ; Gonzalezgranado L10 ; Abbott J11 ; Alzahrani D12 ; Rezaei N13, 14 Show All Authors
Authors
  1. Aydin SE1
  2. Kilic SS2
  3. Aytekin C3
  4. Kumar A4
  5. Porras O5
  6. Kainulainen L6
  7. Kostyuchenko L7
  8. Genel F8
  9. Kutukculer N9
  10. Karaca N9
  11. Gonzalezgranado L10
  12. Abbott J11
  13. Alzahrani D12
  14. Rezaei N13, 14
  15. Baz Z15
  16. Thiel J16, 17
  17. Ehl S17
  18. Marodi L18
  19. Orange JS19
  20. Sawallebelohradsky J1
  21. Keles S20
  22. Holland SM21
  23. Sanal O22
  24. Ayvaz DC22
  25. Tezcan I22
  26. Almousa H23
  27. Alsum Z24
  28. Hawwari A24
  29. Metin A25
  30. Matthesmartin S26
  31. Honig M27
  32. Schulz A27
  33. Picard C28, 29, 30
  34. Barlogis V31
  35. Gennery A32
  36. Ifversen M33
  37. Van Montfrans J34
  38. Kuijpers T35
  39. Bredius R36
  40. Duckers G37
  41. Alherz W38, 39
  42. Pai SY40, 41
  43. Geha R42
  44. Notheis G1
  45. Schwarze CP43
  46. Tavil B44
  47. Azik F44
  48. Bienemann K45
  49. Grimbacher B16, 17
  50. Heinz V1
  51. Gaspar HB46
  52. Aydin R1
  53. Hagl B1
  54. Gathmann B17
  55. Belohradsky BH1
  56. Ochs HD47
  57. Chatila T42
  58. Renner ED1
  59. Su H16
  60. Freeman AF16
  61. Engelhardt K16, 17
  62. Albert MH1, 48
Show Affiliations
Authors Affiliations
  1. 1. Dr. von Haunersches Children’s Hospital, Ludwig-Maximilians-University, Munich, Germany
  2. 2. Department of Pediatric Immunology, Uludag University, Bursa, Turkey
  3. 3. Department of Pediatric Immunology, Dr. Sami Ulus Maternity and Children’s Health and Diseases Training and Research Hospital, Ankara, Turkey
  4. 4. BMT/Immune Deficiency, Cincinnati Children’s Hospital, Cincinatti, OH, United States
  5. 5. Hospital Nacional De Ninos Dr. Carlos Saenz Herrera Servicio de Immunologia y Reumatologia Pediatrica, San Jose, Costa Rica
  6. 6. Department of Pediatrics, Turku University Hospital, Turku, Finland
  7. 7. Pediatric Immunology, Western Ukrainian Specialized Children’s Medical Centre, Lviv, Ukraine
  8. 8. Division of Pediatric Immunology, Behcet Uz State Hospital, Izmir, Turkey
  9. 9. Department of Pediatrics, Ege University, Izmir, Turkey
  10. 10. Pedriatrics, Immunodeficiencies Unit, Hospital 12 Octubre, Madrid, Spain
  11. 11. Fellow, Allergy and Immunology Department of Pediatrics National Jewish Health, University of Colorado, Denver, CO, United States
  12. 12. Pediatric allergy and immunology, King Saud Bin Abdulaziz University for Health Sciences and Department of Pediatrics, National Guard Hospital, King Abdulaziz Medical City–WR, Jeddah, Saudi Arabia
  13. 13. Research Center for Immunodeficiencies, Children’s Medical Center, Tehran, Iran
  14. 14. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  15. 15. Department of Pediatrics, St George Hospital University Medical Center, Beirut, Lebanon
  16. 16. Department of Rheumatology and Clinical Immunology, University Hospital Freiburg, Freiburg, Germany
  17. 17. Center for Chronic Immunodeficiency (CCI), University Medical Centre Freiburg and University of Freiburg, Freiburg, Germany
  18. 18. University of Debrecen, Debrecen, Hungary
  19. 19. Texas Children’s Hospital Center for Human Immunobiology, Houston, TX, United States
  20. 20. Division of Pediatric Allergy and Immunology, Konya Necmettin Erbakan University, Konya, Turkey
  21. 21. Laboratory of Clinical Infectious Diseases, NIAID, National Institutes of Health, Bethesda, MD, United States
  22. 22. Immunology Division, Children’s Hospital, Hacettepe University, Ankara, Turkey
  23. 23. Pediatric Allergy & Immunology, Department of Pediatrics, King Faisal Specialist Hospital & Research Center Riyadh, Riyadh, Saudi Arabia
  24. 24. Department of Genetics, Research Center, MBC 03, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  25. 25. Pediatric Immunology Unit, SB Ankara Diskapi Children’s Hospital, Ankara, Turkey
  26. 26. St. Anna Children’s Hospital, Vienna, Austria
  27. 27. Department of Pediatric Hematology/Oncology, University Childrens Hospital, Ulm, Germany
  28. 28. Study Center for Primary Immunodeficiencies, Necker-Enfant Malades Hospital, Assistance Publique - Hopitaux de Paris (AP-HP), Paris, France
  29. 29. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Imagine Institut, Sorbonne Paris Cite, Paris Descartes University, Paris, France
  30. 30. Pediatric Hematology-Immunology Unit, Necker Enfant Malades Hospital, AP-HP, Paris, France
  31. 31. Department of Paediatric Haematology-Oncology, APHM, La Timone Hospital, Aix-Marseille University, Marseille, France
  32. 32. Institute of Cellular Medicine, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
  33. 33. Rigshospitalet, Copenhagen, Denmark
  34. 34. University Medical Center, Utrecht, Netherlands
  35. 35. Division of Pediatric Hematology, Immunology & Infectious Diseases, Head Emma Children’s Hospital Academic Medical Center (AMC), Amsterdam, Netherlands
  36. 36. Pediatric SCT Unit and Laboratory for Immunology, Department of Pediatrics, LUMC, Leiden, Netherlands
  37. 37. HELIOS Children’s Hospital Krefeld, Krefeld, Germany
  38. 38. Department of Pediatrics, Kuwait University and Allergy and Clinical Immunology Unit, Kuwait City, Kuwait
  39. 39. Department of Pediatrics, Al-Sabah Hospital, Kuwait City, Kuwait
  40. 40. Division of Hematology-Oncology, Boston Children’s Hospital, Boston, MA, United States
  41. 41. Department of Pediatric Hematology-Oncology, Dana-Farber Cancer Institute, Boston, MA, United States
  42. 42. Division of Immunology, Boston Children’s Hospital, Boston, MA, United States
  43. 43. Department of Pediatric Hematology/Oncology, University Childrens Hospital, Tuebingen, Germany
  44. 44. Department of Pediatric Hematology, Ankara Children’s Hematology Oncology Hospital, Ankara, Turkey
  45. 45. Department of Pediatric Hematology/Oncology, University Childrens Hospital, Duesseldorf, Germany
  46. 46. Infection, Immunity, Inflammation and Physiological Medicine, Molecular and Cellular Section, Institute of Child Health, University College London, London, United Kingdom
  47. 47. Center for Immunity and Immunotherapies Seattle Children’s Research Institute, University of Washington, Seattle, WA, United States
  48. 48. Hauner University Childrens Hospital, Lindwurmstr.4, Munich, 80337, Germany

Source: Journal of Clinical Immunology Published:2015


Abstract

Mutations in DOCK8 result in autosomal recessive Hyper-IgE syndrome with combined immunodeficiency (CID). However, the natural course of disease, long-term prognosis, and optimal therapeutic management have not yet been clearly defined. In an international retrospective survey of patients with DOCK8 mutations, focused on clinical presentation and therapeutic measures, a total of 136 patients with a median follow-up of 11.3 years (1.3–47.7) spanning 1693 patient years, were enrolled. Eczema, recurrent respiratory tract infections, allergies, abscesses, viral infections and mucocutaneous candidiasis were the most frequent clinical manifestations. Overall survival probability in this cohort [censored for hematopoietic stem cell transplantation (HSCT)] was 87 % at 10, 47 % at 20, and 33 % at 30 years of age, respectively. Event free survival was 44, 18 and 4 % at the same time points if events were defined as death, life-threatening infections, malignancy or cerebral complications such as CNS vasculitis or stroke. Malignancy was diagnosed in 23/136 (17 %) patients (11 hematological and 9 epithelial cancers, 5 other malignancies) at a median age of 12 years. Eight of these patients died from cancer. Severe, life-threatening infections were observed in 79/136 (58 %); severe non-infectious cerebral events occurred in 14/136 (10 %). Therapeutic measures included antiviral and antibacterial prophylaxis, immunoglobulin replacement and HSCT. This study provides a comprehensive evaluation of the clinical phenotype of DOCK8 deficiency in the largest cohort reported so far and demonstrates the severity of the disease with relatively poor prognosis. Early HSCT should be strongly considered as a potential curative measure. © 2015, Springer Science+Business Media New York.
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