First use of thymus transplantation therapy for FOXN1 deficiency (nude/SCID): a report of 2 cases
First use of thymus transplantation therapy for FOXN1 deficiency (nude/SCID): a report of 2 cases
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DOI：
10.1182/blood-2010-06-292490
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发表时间：
2011-01-13
期刊：
影响因子：
20.3
通讯作者：
Sousa, Ana E.
中科院分区：
文献类型：
--
作者：
Markert, M. Louise;Marques, Jose G.;Sousa, Ana E.
FOXN1缺乏症是一种以肌无力、全脱发和指甲营养不良为特征的原发免疫缺陷。用培养的出生后胸腺组织移植2例FOXN1缺乏症婴儿。受试者1为播散性卡介苗感染，无幼稚标志物的寡克隆T细胞。受试者2有呼吸衰竭，人类疱疹病毒6型感染，细胞减少，没有循环T细胞。受试者在出生后14个月和9个月分别接受了胸腺移植。受试者1在移植前和移植后10个月接受免疫抑制治疗。随访4.9年和2.9年，受试者1、2均无感染并发症发生。受试者1的移植前分枝杆菌病和受试者2的细胞减少症得到解决。受试者2在移植1.6年后发展为自身免疫性甲状腺疾病。两名受试者都产生了功能性免疫。受试者1和受试者2分别有1053/mm(3)和1232/mm(3)CD(3+)细胞，647/mm(3)和868/mm(3)CD(4+)T细胞，213/mm(3)和425/mm(3)初始CD4(+)T细胞，每10万个CD3(+)细胞分别有10200和5700个T细胞受体重排切除周期。他们有正常的CD4T细胞受体β可变谱。两名受试者都出现了抗原特异性的增殖反应，并停止了免疫球蛋白替代。总之，胸腺移植导致了这些FOXN1缺陷婴儿的T细胞重建和功能。(血。2011；117(2)：688-696)
FOXN1 deficiency is a primary immunodeficiency characterized by athymia, alopecia totalis, and nail dystrophy. Two infants with FOXN1 deficiency were transplanted with cultured postnatal thymus tissue. Subject 1 presented with disseminated Bacillus Calmette-Guerin infection and oligoclonal T cells with no naive markers. Subject 2 had respiratory failure, human herpes virus 6 infection, cytopenias, and no circulating T cells. The subjects were given thymus transplants at 14 and 9 months of life, respectively. Subject 1 received immunosuppression before and for 10 months after transplantation. With follow up of 4.9 and 2.9 years, subjects 1 and 2 are well without infectious complications. The pretransplantation mycobacterial disease in subject 1 and cytopenias in subject 2 resolved. Subject 2 developed autoimmune thyroid disease 1.6 years after transplantation. Both subjects developed functional immunity. Subjects 1 and 2 have 1053/mm(3) and 1232/mm(3) CD(3+) cells, 647/mm(3) and 868/mm(3) CD(4+) T cells, 213/mm(3) and 425/mm(3) naive CD4(+) T cells, and 10 200 and 5700 T-cell receptor rearrangement excision circles per 100 000 CD3(+) cells, respectively. They have normal CD4 T-cell receptor beta variable repertoires. Both subjects developed antigen-specific proliferative responses and have discontinued immunoglobulin replacement. In summary, thymus transplantation led to T-cell reconstitution and function in these FOXN1 deficient infants. (Blood. 2011;117(2):688-696)