自身免疫性淋巴增生综合征(ALPS)是一组以早发性淋巴增生为特征的遗传性疾病,自身免疫性血细胞减少症,和对淋巴瘤的易感性。大多数ALPS患者在TNFRSF6基因中携带杂合种系突变。在这项研究中,我们对ALPS和ALPS样综合征患者进行了系统评价.
文献检索在WebofScience中进行,Scopus,和PubMed数据库以查找符合条件的研究。此外,我们在所有纳入论文的参考列表中手工搜索其他研究.人口统计,临床,免疫学,提取并比较ALPS和ALPS样综合征的分子数据。
完全正确,评估了720例ALPS患者(532例遗传确定的ALPS和189例遗传未确定的ALPS)和59例由于ALPS基因以外的基因突变而具有ALPS样表型的患者。在ALPS和ALPS样患者中,脾肿大是最常见的临床表现,其次是自身免疫性血细胞减少症和淋巴结肿大.在其他临床表现中,ALPS样患者的呼吸道感染明显高于ALPS.免疫学分析显示血清IgA水平较低,IgG,与ALPS相比,ALPS样患者的淋巴细胞计数。大多数(85%)具有确定的遗传缺陷的ALPS和ALPS样病例在FAS基因中携带突变。大约三分之一的患者接受了常规或靶向免疫治疗剂的免疫抑制治疗。一小部分患者(3.3%)接受造血干细胞移植并成功植入,除两名患者外,所有患者均在移植后存活。
我们的结果表明,频率为85%的FAS基因是经基因诊断为ALPS表型的患者的主要病因;因此,大多数疑似ALPS患者的遗传缺陷可通过FAS基因突变分析得到证实.
Autoimmune lymphoproliferative syndrome (ALPS) is a group of genetic disorders characterized by early-onset lymphoproliferation, autoimmune cytopenias, and susceptibility to lymphoma. The majority of ALPS patients carry heterozygous germline mutations in the TNFRSF6 gene. In this study, we conducted a systematic
review of patients with ALPS and ALPS-like syndrome.
The literature search was performed in Web of Science, Scopus, and PubMed databases to find eligible studies. Additionally, the reference list of all included papers was hand-searched for additional studies. Demographic, clinical, immunological, and molecular data were extracted and compared between the ALPS and ALPS-like syndrome.
Totally, 720 patients with ALPS (532 genetically determined and 189 genetically undetermined ALPS) and 59 cases with ALPS-like phenotype due to mutations in genes other than ALPS genes were assessed. In both ALPS and ALPS-like patients, splenomegaly was the most common clinical presentation followed by autoimmune cytopenias and lymphadenopathy. Among other clinical manifestations, respiratory tract infections were significantly higher in ALPS-like patients than ALPS. The immunological analysis showed a lower serum level of IgA, IgG, and lymphocyte count in ALPS-like patients compared to ALPS. Most (85%) of the ALPS and ALPS-like cases with determined genetic defects carry mutations in the FAS gene. About one-third of patients received immunosuppressive therapy with conventional or targeted immunotherapy agents. A small fraction of patients (3.3%) received hematopoietic stem cell transplantation with successful engraftment, and all except two patients survived after transplantation.
Our results showed that the FAS gene with 85% frequency is the main etiological cause of genetically diagnosed patients with ALPS phenotype; therefore, the genetic defect of the majority of suspected ALPS patients could be confirmed by mutation analysis of FAS gene.