Transplantation of thymus tissue in complete DiGeorge syndrome
Transplantation of thymus tissue in complete DiGeorge syndrome
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DOI：
10.1056/nejm199910143411603
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发表时间：
1999-10-14
影响因子：
158.5
通讯作者：
Mahaffey, SM
中科院分区：
文献类型：
--
作者：
Markert, ML;Boeck, A;Mahaffey, SM
背景 迪乔治综合征是一种影响心脏、甲状旁腺和胸腺的先天性疾病。在完全型迪乔治综合征中，患者的T细胞功能严重降低。
方法 我们通过移植培养的出生后胸腺组织治疗了5名完全型迪乔治综合征婴儿（年龄1至4个月）。随访评估包括对外周血单核细胞进行免疫表型分析和增殖研究以及对胸腺同种异体移植物进行活检。通过检测T细胞受体基因重排过程中切除的DNA所形成的T细胞受体基因重排切除环，评估外周血中新T细胞的胸腺生成情况。
结果 胸腺组织移植后，5名患者中有4名出现了对有丝分裂原的T细胞增殖反应。2名患者免疫功能恢复并存活；3名患者死于感染或与移植无关的异常情况。存活患者的移植胸腺活检显示形态正常且有活跃的T细胞生成。在3名患者中，大约在移植后4周可检测到供体T细胞，尽管活检或尸检时没有移植物抗宿主病的证据。在1名患者中，移植物内的T细胞发育被证明与外周新生成的T细胞出现相关，并与正常T细胞功能的开始相一致。在1名患者中，有证据表明在移植5年多后胸腺仍有功能且存在CD45RA⁺CD62L⁺T细胞。
结论 在一些患有严重免疫缺陷的完全型迪乔治综合征婴儿中，胸腺组织移植可恢复正常免疫功能。在发生感染并发症之前早期进行胸腺移植可能促进免疫重建成功。（《新英格兰医学杂志》1999年；341卷：1180 - 1189页）（1999年，马萨诸塞州医学协会）
Background The DiGeorge syndrome is a congenital disorder that affects the heart, parathyroid glands, and thymus. In complete DiGeorge syndrome, patients have severely reduced T-cell function.Methods We treated five infants (age, one to four months) with complete DiGeorge syndrome by transplantation of cultured postnatal thymus tissue. Follow-up evaluations included immune phenotyping and proliferative studies of peripheral-blood mononuclear cells plus biopsy of the thymus allograft. Thymic production of new T cells was assessed in peripheral blood by tests for T-cell-receptor recombination excision circles, which are formed from excised DNA during the rearrangement of T-cell-receptor genes.Results After the transplantation of thymus tissue, T-cell proliferative responses to mitogens developed in four of the five patients. Two of the patients survived with restoration of immune function; three patients died from infection or abnormalities unrelated to transplantation. Biopsies of grafted thymus in the surviving patients showed normal morphologic features and active T-cell production. In three patients, donor T cells could be detected about four weeks after transplantation, although there was no evidence of graft-versus-host disease on biopsy or at autopsy. In one patient, the T-cell development within the graft was demonstrated to accompany the appearance of recently developed T cells in the periphery and coincided with the onset of normal T-cell function. In one patient, there was evidence of thymus function and CD45RA+CD62L+ T cells more than five years after transplantation.Conclusions In some infants with profound immunodeficiency and complete DiGeorge syndrome, the transplantation of thymus tissue can restore normal immune function. Early thymus transplantation - before the development of infectious complications - may promote successful immune reconstitution. (N Engl J Med 1999;341:1180-9.) (C)1999, Massachusetts Medical Society.