Department of Pediatrics, Division of Immunology and Allergy, Ankara University Faculty of Medicine, Ankara, Turkey.
Department of Pediatric Immunology, Dr.Sami Ulus Maternity and Children's Health and Diseases Training and Research Hospital, Ankara, Turkey.
Pediatr Allergy Immunol. 2020 Jul;31(5):515-527. doi: 10.1111/pai.13236. Epub 2020 Mar 11.
Biallelic mutations in the dedicator of cytokinesis 8 gene (DOCK8) cause a progressive combined immunodeficiency (CID) characterized by susceptibility to severe viral skin infections, atopic diseases, recurrent respiratory infections, and malignancy. Hematopoietic stem cell transplantation (HSCT) is only curative treatment for the disease. However, there is limited information about long-term outcome of HSCT and its effect to protect against cancer development in DOCK8-deficient patients. In this study, we retrospectively evaluated clinical and immunologic characteristics of 20 DOCK8-deficient patients and outcome of 11 patients who underwent HSCT. We aimed to report the experience of our center and the result of the largest transplantation series of DOCK8 deficiency in our country. Median follow-up time is 71 months (min-max: 16-172) in all patients and 48 months (min-max: 5-84) in transplanted patients. Atopic dermatitis (18/20), recurrent respiratory tract infections (17/20), and food allergy (14/20) were the most frequent clinical manifestations. Failure to thrive (13/20), liver problems (12/20), bronchiectasis (11/20), chronic diarrhea (10/21), and autism spectrum disorders (3/20) were remarkable findings in our series. Elevated IgE level (20/20) and eosinophilia (17/20), low IgM level (15/20), and decreased CD3+ T (10/20) and CD4+ T (11/20) cell count were prominent laboratory findings. HSCT was performed in 11 patients. All patients achieved adequate engraftment and showed improvement in their clinical and immunologic findings. Atopic dermatitis and food allergies improved in all patients, and their dietary restriction was stopped except one patient who was transplanted recently. The frequency of infections was decreased. The overall survival is 91% in HSCT-received patients and 80% in all. HSCT at the earliest possible period with most suitable donor- and patient-specific appropriate conditioning regimen and GvHD prophylaxis is lifesaving for DOCK8 deficiency cases.
DOCK8 基因（DOCK8）的双等位基因突变导致进行性联合免疫缺陷（CID），其特征为易发生严重的病毒性皮肤感染、特应性疾病、反复呼吸道感染和恶性肿瘤。造血干细胞移植（HSCT）是该病唯一的治愈性治疗方法。然而，关于 HSCT 的长期结果及其对预防 DOCK8 缺陷患者癌症发展的影响，信息有限。在这项研究中，我们回顾性评估了 20 例 DOCK8 缺陷患者的临床和免疫学特征，以及 11 例接受 HSCT 的患者的结局。我们旨在报告我们中心的经验和我国最大的 DOCK8 缺陷移植系列的结果。所有患者的中位随访时间为 71 个月（最小-最大：16-172），移植患者的中位随访时间为 48 个月（最小-最大：5-84）。特应性皮炎（18/20）、反复呼吸道感染（17/20）和食物过敏（14/20）是最常见的临床表现。生长迟缓（13/20）、肝脏问题（12/20）、支气管扩张（11/20）、慢性腹泻（10/21）和自闭症谱系障碍（3/20）是我们系列中的显著发现。升高的 IgE 水平（20/20）和嗜酸性粒细胞增多（17/20）、低 IgM 水平（15/20）以及 CD3+ T（10/20）和 CD4+ T（11/20）细胞计数减少是突出的实验室发现。11 例患者接受了 HSCT。所有患者均获得了充分的嵌合，并改善了其临床和免疫学发现。所有患者的特应性皮炎和食物过敏均得到改善，除了最近接受移植的 1 名患者外，他们的饮食限制被取消。感染的频率降低。接受 HSCT 的患者总生存率为 91%，所有患者的总生存率为 80%。对于 DOCK8 缺陷病例，尽早进行 HSCT，并采用最合适的供体和患者特异性适当的预处理方案和 GvHD 预防措施，是挽救生命的关键。
