Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran.
Pediatric Infections Research Center, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Immunol Invest. 2022 Apr;51(3):644-659. doi: 10.1080/08820139.2020.1863982. Epub 2021 Jan 6.
Activated phosphoinositide 3-kinase δ syndrome (APDS) is a recently defined combined primary immunodeficiency disease (PID) characterized by recurrent respiratory tract infections, lymphoproliferation, autoimmunity and lymphoma. Gain-of-function mutations in and loss-of-function of genes lead to APDS1 and APDS2, respectively.
Demographic, clinical, immunological and genetic data were collected from medical records of 15 pediatric patients, who were genetically identified using the whole-exome sequencing method.
Fifteen patients (6 APDS1 and 9 APDS2) were enrolled in this study. Recurrent respiratory tract infections followed by lymphoproliferation and autoimmunity were the most common manifestations (86.7%, 53.3% and 26.7%, respectively). Five patients (33.3%) had a Hyper-IgM-syndrome-like immunoglobulin profile. In the APDS1 group, splice site and missense mutations were found in half of the patients and the C-lobe domain of was the most affected region (50%). In the APDS2 group, splice site mutation was the most frequent mutation (77.8%) and the inter-SH2 domain was the most affected region of (66.7%). Mortality rate was significantly higher in APDS2 group ( = .02) mainly due to chronic lung infections.
Respiratory tract infections and humoral immunodeficiency are commonly the most important complication in pediatric APDS patients, and they can be fatal by ultimately causing catastrophic damage to the structure of lungs. Hence, physicians should be aware of its significance and further work-up of patients with recurrent respiratory tract infections especially in patients with lymphoproliferation. Moreover, delineation of genotype-phenotype associations with disease severity could be helpful in the timely application of appropriate management and patients' survival.
活化的磷酯酰肌醇 3-激酶 δ 综合征（APDS）是一种最近定义的联合原发性免疫缺陷病（PID），其特征是复发性呼吸道感染、淋巴增生、自身免疫和淋巴瘤。 和 基因的功能获得性突变和功能丧失分别导致 APDS1 和 APDS2。
从通过全外显子组测序方法进行基因鉴定的 15 名儿科患者的病历中收集人口统计学、临床、免疫学和遗传学数据。
本研究纳入了 15 名患者（6 例 APDS1 和 9 例 APDS2）。复发性呼吸道感染继之以淋巴增生和自身免疫是最常见的表现（分别为 86.7%、53.3%和 26.7%）。5 名患者（33.3%）具有高免疫球蛋白 M 综合征样免疫球蛋白谱。在 APDS1 组中，一半的患者存在剪接位点和错义突变， 基因的 C 结构域是受影响最严重的区域（50%）。在 APDS2 组中，最常见的突变为剪接位点突变（77.8%）， 基因的跨 SH2 结构域是受影响最严重的区域（66.7%）。APDS2 组的死亡率明显更高（=0.02），主要是由于慢性肺部感染。
呼吸道感染和体液免疫缺陷是儿科 APDS 患者最常见的重要并发症，最终会导致肺部结构灾难性损害，从而导致死亡。因此，医生应该意识到其重要性，并进一步对复发性呼吸道感染的患者进行检查，尤其是在有淋巴增生的患者中。此外，明确基因型-表型与疾病严重程度的关联可能有助于及时应用适当的管理措施并提高患者的生存率。
