Activated Phosphoinositide 3-Kinase δ Syndrome: a Large Pediatric Cohort from a Single Center in China
Activated Phosphoinositide 3-Kinase δ Syndrome: a Large Pediatric Cohort from a Single Center in China
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DOI：
10.1007/s10875-022-01218-4
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发表时间：
2022-03-16
影响因子：
9.1
通讯作者：
Zhao, Xiaodong
中科院分区：
文献类型：
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作者：
Qiu, Luyao;Wang, Yanping;Zhao, Xiaodong
目的 活化磷酸肌醇 3-激酶 δ 综合征 (APDS) 是一种原发性免疫缺陷病，于 2013 年首次被描述，由 PIK3CD 或 PIK3R1 功能获得性突变引起，其特征为反复呼吸道感染、淋巴细胞增殖、疱疹病毒感染、自身免疫和肠病。我们试图在大型基因定义的中国儿科队列中回顾 APDS 的临床表型、免疫学特征、治疗和预后。方法回顾了 40 名 APDS 患者的临床记录、放射学检查和实验室检查。通过电话联系患者，跟进他们的现状。结果肺部感染和淋巴细胞增生是该队列中最常见的并发症。 3 名（10.3%）和 5 名（12.5%）患者分别患有卡介苗引起的局部肉芽肿性炎症和结核感染。 27 名患者（67.5%）患有自身免疫性疾病，而恶性肿瘤（7.5%）相对较少见。我们队列中的大多数患者接受了抗感染预防、免疫球蛋白替代和免疫抑制治疗（例如糖皮质激素或雷帕霉素给药）的联合治疗。 12例患者接受了造血干细胞移植（HSCT），预后满意。结论 APDS的临床谱具有异质性。该队列中局部 BCG 诱导的肉芽肿性炎症和结核病的发生率较高，表明 APDS 患者对分枝杆菌具有易感性。雷帕霉素可有效改善淋巴细胞增殖和血细胞减少。对于有严重并发症且对其他治疗反应不佳的患者来说，HSCT 是一种选择。
Purpose Activated phosphoinositide 3-kinase delta syndrome (APDS) is a primary immunodeficiency first described in 2013, which is caused by gain-of-function mutations in PIK3CD or PIK3R1, and characterized by recurrent respiratory tract infections, lymphoproliferation, herpesvirus infection, autoimmunity, and enteropathy. We sought to review the clinical phenotypes, immunological characteristics, treatment, and prognosis of APDS in a large genetically defined Chinese pediatric cohort.Methods Clinical records, radiology examinations, and laboratory investigations of 40 APDS patients were reviewed. Patients were contacted via phone call to follow up their current situation.Results Sinopulmonary infections and lymphoproliferation were the most common complications in this cohort. Three (10.3%) and five (12.5%) patients suffered localized BCG-induced granulomatous inflammation and tuberculosis infection, respectively. Twenty-seven patients (67.5%) were affected by autoimmunity, while malignancy (7.5%) was relatively rare to be seen. Most patients in our cohort took a combined treatment of anti-infection prophylaxis, immunoglobulin replacement, and immunosuppressive therapy such as glucocorticoid or rapamycin administration. Twelve patients underwent hematopoietic stem cell transplantation (HSCT) and had a satisfying prognosis.Conclusion Clinical spectrum of APDS is heterogeneous. This cohort's high incidence of localized BCG-induced granulomatous inflammation and tuberculosis indicates Mycobacterial susceptibility in APDS patients. Rapamycin is effective in improving lymphoproliferation and cytopenia. HSCT is an option for those who have severe complications and poor response to other treatments.