Postnatal thymus transplantation with immunosuppression as treatment for DiGeorge syndrome
Postnatal thymus transplantation with immunosuppression as treatment for DiGeorge syndrome
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DOI：
10.1182/blood-2003-08-2984
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发表时间：
2004-10-15
期刊：
影响因子：
20.3
通讯作者：
Skinner, MA
中科院分区：
文献类型：
--
作者：
Markert, ML;Alexieff, MJ;Skinner, MA
完全性DiGeorge综合征是一种以无胸腺、甲状旁腺功能减退和心脏缺陷为特征的致命性先天性疾病。不到一半的患者是22 q11半合子。本研究的目的是评估出生后胸腺移植后的免疫抑制是否会导致6例在移植时具有宿主T细胞的婴儿患者的T细胞功能。所有婴儿的近期胸腺移行细胞（CD 3（+）CD 45 RA（+）CD 62 L（+））每立方毫米（mm 3）少于50个，并且所有婴儿都对有丝分裂原植物血凝素有一定的增殖反应。4名婴儿出现皮疹、淋巴结病和外周血T细胞寡克隆群。随访15 ~ 30个月，6例中5例存活。5例存活患者的平均宿主CD 3（+）T细胞数为983/ mm 3（范围536/mm 3 - 1574/mm 3），平均近期胸腺移出数为437/mm 3（范围196/mm 3 - 785/mm 3），对植物血红素的增殖反应正常（随访376 - 873天）。在出现寡克隆T细胞的患者中，TCR库变为多克隆。所有患者移植物活检均显示胸腺生成。胸腺球蛋白治疗后的出生后胸腺移植显示出治疗完全DiGeorge综合征的婴儿的希望，这些婴儿对有丝分裂原有显著的增殖反应或出现皮疹、淋巴结病和寡克隆T细胞。
Complete DiGeorge syndrome is a fatal congenital disorder characterized by athymia, hypoparathyroidism, and heart defects. Less than half of patients are 22q11 hemizygous. The goal of this study was to assess if immune suppression followed by postnatal thymus transplantation would lead to T-cell function in 6 infant patients who had host T cells at the time of transplantation. All infants had fewer than 50 recent thymic emigrants (CD3(+)CD45RA(+)CD62L(+)) per cubic millimeter (mm(3)) and all had some proliferative response to the mitogen phytohemagglutinin. Four infants had rash, lymphadenopathy, and oligoclonal populations of T cells in the periphery. Five of 6 patients are alive at the follow-up interval of 15 months to 30 months. The 5 surviving patients developed a mean of 983 host CD3(+) T cells/ mm(3) (range, 536/mm(3)-1574/mm(3)), a mean of 437 recent thymic emigrants/mm(3) (range, 196/mm(3)-785/mm(3)), and normal proliferative responses to phytohema-glutinin (follow-up from day 376 to day 873). The TCR repertoire became polyclonal in patients who presented with oligoclonal T cells. All patients had thymopoiesis on allograft biopsy. Postnatal thymus transplantation after treatment with Thymoglobulin shows promise as therapy for infants with complete DiGeorge syndrome who have significant proliferative responses to mitogens or who develop rash, lymphadenopathy, and oligoclonal T cells.