Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran.
Alborz Office of USERN, Universal Scientific Education and Research Network (USERN), Alborz University of Medical Sciences, Karaj, Iran.
Front Immunol. 2020 May 5;11:831. doi: 10.3389/fimmu.2020.00831. eCollection 2020.
Zeta-Chain Associated Protein Kinase 70 kDa (ZAP-70) deficiency is a rare combined immunodeficiency (CID) caused by recessive homozygous/compound heterozygous loss-of-function mutations in the gene. Patients with ZAP-70 deficiency present with a variety of clinical manifestations, particularly recurrent respiratory infections and cutaneous involvements. Therefore, a systematic review of ZAP-70 deficiency is helpful to achieve a comprehensive view of this disease. We searched PubMed, Web of Science, and Scopus databases for all reported ZAP-70 deficient patients and screened against the described eligibility criteria. A total of 49 ZAP-70 deficient patients were identified from 33 articles. For all patients, demographic, clinical, immunologic, and molecular data were collected. ZAP-70 deficient patients have been reported in the literature with a broad spectrum of clinical manifestations including recurrent respiratory infections (81.8%), cutaneous involvement (57.9%), lymphoproliferation (32.4%), autoimmunity (19.4%), enteropathy (18.4%), and increased risk of malignancies (8.1%). The predominant immunologic phenotype was low CD8+ T cell counts (97.9%). Immunologic profiling showed defective antibody production (57%) and decreased lymphocyte responses to mitogenic stimuli such as phytohemagglutinin (PHA) (95%). Mutations of the gene were located throughout the gene, and there was no mutational hotspot. However, most of the mutations were located in the kinase domain. Hematopoietic stem cell transplantation (HSCT) was applied as the major curative treatment in 25 (51%) of the patients, 18 patients survived transplantation, while two patients died and three required a second transplant in order to achieve full remission. Newborns with consanguineous parents, positive family history of CID, and low CD8+ T cell counts should be considered for ZAP-70 deficiency screening, since early diagnosis and treatment with HSCT can lead to a more favorable outcome. Based on the current evidence, there is no genotype-phenotype correlation in ZAP-70 deficient patients.
Z 链相关蛋白激酶 70kDa（ZAP-70）缺陷症是一种罕见的联合免疫缺陷（CID），由 基因隐性纯合/复合杂合失活突变引起。ZAP-70 缺陷症患者表现出多种临床表现，特别是反复呼吸道感染和皮肤受累。因此，对 ZAP-70 缺陷症进行系统综述有助于全面了解该疾病。我们在 PubMed、Web of Science 和 Scopus 数据库中搜索了所有报道的 ZAP-70 缺乏症患者，并根据描述的纳入标准进行筛选。从 33 篇文章中确定了 49 例 ZAP-70 缺乏症患者。所有患者均收集了人口统计学、临床、免疫学和分子数据。文献中报道的 ZAP-70 缺乏症患者具有广泛的临床表现，包括反复呼吸道感染（81.8%）、皮肤受累（57.9%）、淋巴组织增生（32.4%）、自身免疫（19.4%）、肠病（18.4%）和恶性肿瘤风险增加（8.1%）。主要的免疫表型是 CD8+T 细胞计数低（97.9%）。免疫分析显示抗体产生缺陷（57%），对植物血凝素（PHA）等有丝分裂刺激物的淋巴细胞反应降低（95%）。 基因的突变位于整个基因中，没有突变热点。然而，大多数突变位于激酶结构域。造血干细胞移植（HSCT）是 25 例（51%）患者的主要治疗方法，18 例患者存活移植，2 例患者死亡，3 例患者需要第二次移植以达到完全缓解。对于来自近亲的新生儿、CID 阳性家族史和 CD8+T 细胞计数低的患者，应考虑进行 ZAP-70 缺陷筛查，因为早期诊断和 HSCT 治疗可以带来更好的预后。根据目前的证据，ZAP-70 缺陷症患者没有基因型-表型相关性。
