DOCK8 Deficiency: Clinical and Immunological Phenotype and Treatment Options - a Review of 136 Patients

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• 作者：Susanne E. Aydin ; Sara Sebnem Kilic ; Caner Aytekin…
• 关键词：DOCK8 deficiency ; combined immunodeficiency ; hyper ; IgE syndrome ; natural outcome
• 刊名：Journal of Clinical Immunology
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：35
• 期：2
• 页码：189-198
• 全文大小：513 KB
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  9. Zhang, Q, Davis, JC, Lamborn, IT, Freeman, AF, Jing, H, Favreau, AJ (2009) Combined immunodeficiency associated with DOCK8 mutations. N Engl J Med 361: pp. 2046-55 CrossRef
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  11. Keles, S, Jabara, HH, Reisli, I, McDonald, DR, Barlan, I, Hanna-Wakim, R (2014) Plasmacytoid dendritic cell depletion in DOCK8 deficiency: rescue of severe herpetic infections with IFN-alpha 2b therapy. J Allergy Clin Immunol 133: pp. 1753-1755 CrossRef
  12. Papan, C, Hagl, B, Heinz, V, Albert, MH, Ehrt, O, Sawalle-Belohradsky, J (2014) Beneficial IFN-alpha treatment of tumorous herpes simplex blepharoconjunctivitis in dedicator of cytokinesis 8 deficiency. J Allergy Clin Immunol 133: pp. 1456-8 CrossRef
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  14. Gatz, SA, Benninghoff, U, Schutz, C, Schulz, A, Honig, M, Pannicke, U (2011) Curative treatment of autosomal-recessive hyper-IgE syndrome by hematopoietic cell transplantation. Bone Marrow Transplant 46: pp. 552-6 CrossRef
  15. Boztug, H, Karitnig-Weiss, C, Ausserer, B, Renner, ED, Albert, MH, Sawalle-Belohradsky, J (2012) Clinical and immunological correction of DOCK8 deficiency by allogeneic hematopoietic stem cell transplantation following a reduced toxicity conditioning regimen. Pediatr Hematol Oncol 29: pp. 585-94
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  17. Ghosh, S, Schuster, FR, Adams, O, Babor, F, Borkhardt, A, Comoli, P (2014) Haploidentical stem cell transplantation in DOCK8 deficiency - successful control of pre-existing severe viremia with a TCRass/CD19-
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Immunology
  Infectious Diseases
  Internal Medicine
  Medical Microbiology
  
• 出版者：Springer Netherlands
• ISSN：1573-2592

文摘

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 (1.3-7.7) 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.