Naviglio Samuele, Soncini Elena, Vairo Donatella, Lanfranchi Arnalda, Badolato Raffaele, Porta Fulvio
Department of Medicine, Surgery, and Health Sciences, University of Trieste, Trieste, Italy.
Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy.
J Clin Immunol. 2017 Oct;37(7):701-706. doi: 10.1007/s10875-017-0430-6. Epub 2017 Aug 16.
Complete signal transducer and activator of transcription 1 (STAT1) deficiency is a rare autosomal recessive condition characterized by impairment of intracellular signaling from both type I and type II interferons (IFN). Affected patients are prone to early severe mycobacterial and viral infections, which usually result in death before 18 months of age. We previously reported a patient affected by complete STAT1 deficiency who underwent hematopoietic stem cell transplantation (HSCT). Here, we describe the transplantation procedures and long-term outcomes.
The patient, who had suffered multiple life-threatening mycobacterial and viral infections in the first years of life, underwent HSCT at 4 years of age from a partially matched (HLA compatibility 8/10) unrelated donor after a myeloablative conditioning regimen consisting of busulfan, cyclophosphamide, and anti-thymocyte globulin.
Hematological reconstitution was detected at d+15, with full donor engraftment demonstrated by molecular analysis of leukocytes. Several complications occurred in the post-transplantation phase, including acute graft versus host disease, posterior reversible encephalopathy, thrombotic thrombocytopenic purpura, bilateral keratoconjunctivitis with complete loss of vision, and chronic lower limb lymphedema. Analysis of STAT1 in CD3 cells at 90 and 120 days after HSCT by flow cytometry showed normal STAT1 phosphorylation levels in response to IFN-α.
Notably, no severe infections occurred after discharge (day + 90) during a 9-year follow-up, suggesting that normal response to IFNs in hematopoietic cells is sufficient to provide protection in humans.
完全性信号转导子与转录激活子1（STAT1）缺陷是一种罕见的常染色体隐性疾病，其特征为I型和II型干扰素（IFN）的细胞内信号传导受损。受影响的患者易患早期严重的分枝杆菌和病毒感染，通常在18个月龄前死亡。我们之前报道了一名受完全性STAT1缺陷影响的患者接受了造血干细胞移植（HSCT）。在此，我们描述移植过程和长期结果。
该患者在生命的头几年遭受了多次危及生命的分枝杆菌和病毒感染，4岁时在接受了由白消安、环磷酰胺和抗胸腺细胞球蛋白组成的清髓预处理方案后，从一名部分匹配（HLA配型8/10）的无关供体接受了HSCT。
在移植后第15天检测到血液学重建，通过白细胞分子分析证实供体完全植入。移植后阶段出现了几种并发症，包括急性移植物抗宿主病、后部可逆性脑病、血栓性血小板减少性紫癜、双侧角膜结膜炎伴完全失明以及慢性下肢淋巴水肿。通过流式细胞术分析HSCT后90天和120天CD3细胞中的STAT1，显示对IFN-α的反应中STAT1磷酸化水平正常。
值得注意的是，在9年的随访期间，出院后（第90天）未发生严重感染，这表明造血细胞对IFN的正常反应足以在人类中提供保护。
