PDF(Pubmed)
Abstract：
Congenital athymia can present with severe T cell lymphopenia (TCL) in the newborn period, which can be detected by decreased T cell receptor excision circles (TRECs) on newborn screening (NBS). The most common thymic stromal defect causing selective TCL is 22q11.2 deletion syndrome (22q11.2DS). T-box transcription factor 1 (TBX1), present on chromosome 22, is responsible for thymic epithelial development. Single variants in TBX1 causing haploinsufficiency cause a clinical syndrome that mimics 22q11.2DS. Definitive therapy for congenital athymia is allogeneic thymic transplantation. However, universal availability of such therapy is limited. We present a patient with early diagnosis of congenital athymia due to TBX1 haploinsufficiency. While evaluating for thymic transplantation, she developed Omenn Syndrome (OS) and life-threatening adenoviremia. Despite treatment with anti-virals and cytotoxic T lymphocytes (CTLs), life threatening adenoviremia persisted. Given the imminent need for rapid establishment of T cell immunity and viral clearance, the patient underwent an unmanipulated matched sibling donor (MSD) hematopoietic cell transplant (HCT), ultimately achieving post-thymic donor-derived engraftment, viral clearance, and immune reconstitution. This case illustrates that because of the slower immune recovery that occurs following thymus transplantation and the restricted availability of thymus transplantation globally, clinicians may consider CTL therapy and HCT to treat congenital athymia patients with severe infections.
摘要：
先天性肾病可在新生儿期间出现严重的T细胞淋巴细胞减少症（TCL），可以通过新生儿筛查（NBS）中T细胞受体切除环（TRECs）的减少来检测。导致选择性TCL的最常见胸腺基质缺损是22q11.2缺失综合征(22q11.2DS)。T-box转录因子1(TBX1),存在于22号染色体上，负责胸腺上皮发育。TBX1中导致单倍体功能不全的单个变体引起模拟22q11.2DS的临床综合征。先天性无精症的决定性治疗是同种异体胸腺移植。然而,这种疗法的普遍可用性是有限的。我们介绍了一名因TBX1单倍功能不全而早期诊断为先天性异常的患者。在评估胸腺移植时，她出现了Omenn综合征（OS）和危及生命的腺病毒血症。尽管用抗病毒药物和细胞毒性T淋巴细胞（CTL）治疗，危及生命的腺病毒血症持续存在。鉴于迫切需要快速建立T细胞免疫和病毒清除，患者接受了未经处理的同胞供体（MSD）造血细胞移植（HCT），最终实现胸腺后供体来源的移植，病毒清除,和免疫重建。该病例说明，由于胸腺移植后免疫恢复较慢，而且胸腺移植在全球范围内的可用性有限，临床医生可考虑CTL治疗和HCT治疗严重感染的先天性无创性患者.
