Hematopoietic stem cell transplantation recovers insulin deficiency in type 1 diabetes mellitus associated with IPEX syndrome
Hematopoietic stem cell transplantation recovers insulin deficiency in type 1 diabetes mellitus associated with IPEX syndrome
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DOI：
10.1111/pedi.12895
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发表时间：
2019-07-24
影响因子：
3.4
通讯作者：
Morio, Tomohiro
中科院分区：
文献类型：
--
作者：
Yamauchi, Takeru;Takasawa, Kei;Morio, Tomohiro
免疫失调、多内分泌病、肠病和x连锁综合征（IPEX）是一种由FOXP3功能障碍引起的自身免疫性疾病，其导致调节性T-(Treg)细胞功能障碍和随后的自身免疫，包括1型糖尿病（T1D）。目前，同种异体造血干细胞移植（HSCT）是治疗IPEX综合征的一种潜在的治疗方法，但不适合T1D。通常，在胰腺β细胞完全丢失后，HSCT不能改善T1D的预后。在这里，我们报告了一名16岁的青少年，患有晚发性FOXP3 R347H突变相关的IPEX综合征伴T1D，在HSCT后胰岛素依赖性得到改善。该患者患有胰岛素依赖型糖尿病，HSCT前1个月胰岛素剂量为1.28 U/kg/天。虽然HSCT前的葡萄糖稳态结果显示胰岛素分泌受损和低δ c肽免疫反应性（CPR, 1.0 ng/mL），但患者在HSCT后15个月停止胰岛素输注并保持血糖正常，并在HSCT后20个月改善δ CPR （3.4 ng/mL）后β细胞功能正常。本病例表明，针对t1d相关IPEX综合征的HSCT可改善Treg缺乏症并防止β细胞的消除。我们推测，从T1D发病到HSCT的时间可能影响IPEX T1D的治疗效果，在DM发病前或发病后立即进行HSCT的早期干预可以挽救β细胞，完全缓解T1D。我们的研究不仅阐述了IPEX治疗T1D的治疗策略，而且还阐述了一般T1D的发病机制。
Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome is an autoimmune disorder caused by the dysfunction of FOXP3, which leads to regulatory T-(Treg) cell dysfunction and subsequently autoimmunity including type 1 diabetes mellitus (T1D). Presently, allogeneic hematopoietic stem cell transplantation (HSCT) is a potential curative therapy for IPEX syndrome, but not for T1D. Generally, after complete loss of pancreatic beta-cells, HSCT cannot improve the prognosis of T1D. Here, we report the case of a 16-year-old adolescent with late-onset of FOXP3 R347H mutation associated IPEX syndrome with T1D, where insulin dependency was ameliorated following HSCT. This patient with insulin-dependent diabetes mellitus required insulin dosage of 1.28 U/kg/day for 1 month before HSCT. Although the results of glucose homeostasis before HSCT revealed impaired insulin secretion and low Delta C-peptide immunoreactivity (CPR, 1.0 ng/mL), the patient withdrew insulin infusion and remained euglycemic at 15 months after HSCT, and had normal beta-cell function with improved Delta CPR (3.4 ng/mL) at 20 months after HSCT. The present case suggests that HSCT for T1D-associated IPEX syndrome improves Treg deficiency and prevents elimination of beta-cells. We speculate that the period from the onset of T1D to HSCT could affect the therapeutic efficacy for T1D with IPEX, and early intervention with HSCT before or immediately after the onset of DM can rescue beta-cells and remit T1D completely. Our study elaborates not only the therapeutic strategy for T1D with IPEX, but also the pathogenic mechanism in general T1D.