Respiratory Manifestations of the Activated Phosphoinositide 3-Kinase Delta Syndrome.
Respiratory Manifestations of the Activated Phosphoinositide 3-Kinase Delta Syndrome.
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DOI：
10.3389/fimmu.2018.00338
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发表时间：
2018
影响因子：
7.3
通讯作者：
Chandra A
中科院分区：
文献类型：
--
作者：
Condliffe AM;Chandra A
活化磷酸肌苷激酶δ综合征（APDS），也称为p110δ活化突变引起衰老T细胞，淋巴结病和免疫缺陷（PASLI），是由磷酸肌苷激酶（PI3K）基因PIK3CD（编码p110δ: APDS1或PASLI- cd）和PIK3R1（编码p85α: APDS2或PASLI- r1）的功能获得性突变引起的联合免疫缺陷综合征。虽然该病在临床上具有异质性，但呼吸道症状和并发症几乎是普遍的，而且往往很严重。耳部、鼻窦和上呼吸道和下呼吸道感染是APDS最早和最常见的表现，继发于呼吸道病毒和典型的B细胞功能缺陷的细菌病原体。终末器官损伤以小气道疾病和支气管扩张的形式经常使APDS并发症，但尽管有记录的T细胞缺陷，很少观察到机会性感染。抗菌素（主要是抗生素）预防和/或免疫球蛋白替代已被广泛用于减少APDS呼吸道感染的频率和严重程度，但证实这些干预措施有效性的结果数据有限。尽管采取了这些措施，但APDS患者经常受到良性淋巴增生性疾病的困扰，这些疾病可能在呼吸系统中表现为扁桃体/腺样体肿大、纵隔淋巴结病或粘膜结节性淋巴样增生，可能导致气道阻塞并使感染表型复杂化。据报道，雷帕霉素和PI3Kδ抑制剂治疗对良性淋巴细胞增殖有益，但造血干细胞移植（理想情况下在永久性气道损伤建立之前进行）仍然是APDS唯一的治疗方法。
The activated phosphoinositide 3-kinase δ syndrome (APDS), also known as p110δ-activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency (PASLI), is a combined immunodeficiency syndrome caused by gain-of-function mutations in the phosphoinositide 3-kinase (PI3K) genes PIK3CD (encoding p110δ: APDS1 or PASLI-CD) and PIK3R1 (encoding p85α: APDS2 or PASLI-R1). While the disease is clinically heterogeneous, respiratory symptoms and complications are near universal and often severe. Infections of the ears, sinuses, and upper and lower respiratory tracts are the earliest and most frequent manifestation of APDS, secondary to both respiratory viruses and to bacterial pathogens typical of defective B cell function. End organ damage in the form of small airways disease and bronchiectasis frequently complicates APDS, but despite documented T cell defects, opportunistic infections have rarely been observed. Antimicrobial (principally antibiotic) prophylaxis and/or immunoglobulin replacement have been widely used to reduce the frequency and severity of respiratory infection in APDS, but outcome data to confirm the efficacy of these interventions are limited. Despite these measures, APDS patients are often afflicted by benign lymphoproliferative disease, which may present in the respiratory system as tonsillar/adenoidal enlargement, mediastinal lymphadenopathy, or mucosal nodular lymphoid hyperplasia, potentially causing airways obstruction and compounding the infection phenotype. Treatment with rapamycin and PI3Kδ inhibitors has been reported to be of benefit in benign lymphoproliferation, but hematopoietic stem cell transplantation (ideally undertaken before permanent airway damage is established) remains the only curative treatment for APDS.