National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
Department of Hematology and Oncology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
J Clin Immunol. 2024 Jun 19;44(7):152. doi: 10.1007/s10875-024-01753-2.
A boy with primary immunodeficiency, caused by a tyrosine kinase 2 (TYK2) mutation, presented with immune defects and a lifelong history of severe infections. Our aim was to determine whether allogeneic hematopoietic stem cell transplantation (HSCT) could restore the patient's immune defenses and reduce susceptibility to infection. In the absence of a suitable HLA-matched blood relative to act as a donor, the patient received an allogeneic HSCT from unrelated donors. The patient's clinical data were analyzed in the Children's Hospital of Chongqing Medical University (Chongqing, China) before transplantation and during the 4-year follow-up period using a combination of western blotting (e.g., TYK2 and STAT levels), qRT-PCR (e.g., T cell receptor rearrangement excision circles, kappa deletion element recombination circles, and TYK2 transcript levels), and flow cytometry (e.g., lymphocyte subpopulations and CD107α secretion). We found that HSCT significantly reduced the incidence of severe infections, restored normal TKY2 levels, and reversed defects such as impaired JAK/STAT signaling in response to interferon-α or interleukin-10 treatment. Although the patient did not develop acute graft-versus-host disease (GVHD) after transplantation, he did experience chronic GVHD symptoms in a number of organs, which were effectively managed. Our findings suggest that HSCT is a feasible strategy for reconstituting the immune system in TYK2-deficient patients; however, the factors associated with GVHD and autoimmune thyroiditis development in TYK2-deficient patients undergoing HSCT warrant further investigation.
一名酪氨酸激酶 2 (TYK2) 突变导致原发性免疫缺陷的男孩，表现出免疫缺陷和终生严重感染史。我们的目的是确定异基因造血干细胞移植（HSCT）是否可以恢复患者的免疫防御能力并降低感染易感性。由于缺乏合适的 HLA 匹配的血缘关系供体，该患者接受了来自无关供体的异基因 HSCT。在移植前和 4 年随访期间，我们在重庆医科大学儿童医院（中国重庆）使用 Western blot（例如 TYK2 和 STAT 水平）、qRT-PCR（例如 T 细胞受体重排切除环、kappa 缺失元件重组环和 TYK2 转录本水平）和流式细胞术（例如淋巴细胞亚群和 CD107α 分泌）分析了患者的临床数据。我们发现 HSCT 显著降低了严重感染的发生率，恢复了正常的 TKY2 水平，并逆转了干扰素-α或白细胞介素-10 治疗时 JAK/STAT 信号传导受损等缺陷。尽管该患者在移植后未发生急性移植物抗宿主病（GVHD），但他确实在多个器官中出现了慢性 GVHD 症状，这些症状得到了有效控制。我们的研究结果表明，HSCT 是恢复 TYK2 缺陷患者免疫系统的一种可行策略；然而，HSCT 后 TYK2 缺陷患者发生 GVHD 和自身免疫性甲状腺炎的相关因素仍需进一步研究。
