Selective expansion of donor-derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome
Selective expansion of donor-derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome
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DOI：
10.1111/petr.12184
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发表时间：
2014-02-01
影响因子：
1.3
通讯作者：
Kure, Shigeo
中科院分区：
文献类型：
--
作者：
Horino, Satoshi;Sasahara, Yoji;Kure, Shigeo
Ipex综合征是一种罕见的致命性疾病，由于Forkhead box蛋白3基因的先天突变而导致调节性T细胞(Treg)缺失。在这里，我们报告了一例IPEX综合征的患者，接受了RIC治疗，随后接受了来自一个HLA相合的同胞供者的异基因骨髓移植。我们可以实现植入，方案相关的毒性耐受性很好。虽然患者处于混合嵌合体状态，外周血中供者细胞比例较低，但仍可观察到以CD4+CD25+Foxp3+细胞为指标的Tregs选择性持续扩增。临床症状的改善与供体来源的Tregs的扩大和抗Villin自身抗体的消失有关，这与IPEX综合征的胃肠道症状的发病机制有关。这一临床观察表明，供者来源的Tregs在IPEX综合征患者中具有选择性生长优势，甚至在异基因骨髓移植后的混合嵌合体中也具有选择性生长优势，有助于控制因Tregs缺陷引起的临床症状。
IPEX syndrome is a rare and fatal disorder caused by absence of regulatory T cells (Tregs) due to congenital mutations in the Forkhead box protein 3 gene. Here, we report a patient with IPEX syndrome treated with RIC followed by allogeneic BMT from an HLA-matched sibling donor. We could achieve engraftment and regimen-related toxicity was well tolerated. Although the patient was in mixed chimera and the ratio of donor cells in whole peripheral blood remained relatively low, selective and sustained expansion of Tregs determined as CD4+CD25+Foxp3+ cells was observed. Improvement in clinical symptoms was correlated with expansion of donor-derived Tregs and disappearance of anti-villin autoantibody, which was involved in the pathogenesis of gastrointestinal symptoms in IPEX syndrome. This clinical observation suggests that donor-derived Tregs have selective growth advantage in patients with IPEX syndrome even in mixed chimera after allogeneic BMT and contribute to the control of clinical symptoms caused by the defect of Tregs.