完全性DiGeorge综合征的胸腺移植：欧洲经验
Thymus transplantation for complete DiGeorge syndrome: European experience.
作者信息
Davies E Graham, Cheung Melissa, Gilmour Kimberly, Maimaris Jesmeen, Curry Joe, Furmanski Anna, Sebire Neil, Halliday Neil, Mengrelis Konstantinos, Adams Stuart, Bernatoniene Jolanta, Bremner Ronald, Browning Michael, Devlin Blythe, Erichsen Hans Christian, Gaspar H Bobby, Hutchison Lizzie, Ip Winnie, Ifversen Marianne, Leahy T Ronan, McCarthy Elizabeth, Moshous Despina, Neuling Kim, Pac Malgorzata, Papadopol Alina, Parsley Kathryn L, Poliani Luigi, Ricciardelli Ida, Sansom David M, Voor Tiia, Worth Austen, Crompton Tessa, Markert M Louise, Thrasher Adrian J
机构信息
Infection, Immunity and Inflammation Theme, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; Department of Immunology, Great Ormond Street Hospital, London, United Kingdom.
Infection, Immunity and Inflammation Theme, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
出版信息
J Allergy Clin Immunol. 2017 Dec;140(6):1660-1670.e16. doi: 10.1016/j.jaci.2017.03.020. Epub 2017 Apr 8.
BACKGROUND
Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS).
METHODS
Twelve patients with cDGS underwent transplantation with allogeneic cultured thymus.
OBJECTIVE
We sought to confirm and extend the results previously obtained in a single center.
RESULTS
Two patients died of pre-existing viral infections without having thymopoiesis, and 1 late death occurred from autoimmune thrombocytopenia. One infant had septic shock shortly after transplantation, resulting in graft loss and the need for a second transplant. Evidence of thymopoiesis developed from 5 to 6 months after transplantation in 10 patients. Median circulating naive CD4 counts were 44 × 10/L (range, 11-440 × 10/L) and 200 × 10/L (range, 5-310 × 10/L) at 12 and 24 months after transplantation and T-cell receptor excision circles were 2,238/10 T cells (range, 320-8,807/10 T cells) and 4,184/10 T cells (range, 1,582-24,596/10 T cells). Counts did not usually reach normal levels for age, but patients were able to clear pre-existing infections and those acquired later. At a median of 49 months (range, 22-80 months), 8 have ceased prophylactic antimicrobials, and 5 have ceased immunoglobulin replacement. Histologic confirmation of thymopoiesis was seen in 7 of 11 patients undergoing biopsy of transplanted tissue, including 5 showing full maturation through to the terminal stage of Hassall body formation. Autoimmune regulator expression was also demonstrated. Autoimmune complications were seen in 7 of 12 patients. In 2 patients early transient autoimmune hemolysis settled after treatment and did not recur. The other 5 experienced ongoing autoimmune problems, including thyroiditis (3), hemolysis (1), thrombocytopenia (4), and neutropenia (1).
CONCLUSIONS
This study confirms the previous reports that thymus transplantation can reconstitute T cells in patients with cDGS but with frequent autoimmune complications in survivors.
背景
胸腺移植是治疗无胸腺完全性迪格奥尔格综合征（cDGS）的一种有前景的策略。
方法
12例cDGS患者接受了同种异体培养胸腺移植。
目的
我们试图证实并扩展先前在单一中心获得的结果。
结果
2例患者死于移植前已存在的病毒感染，未发生胸腺生成，1例晚期死亡因自身免疫性血小板减少症。1例婴儿在移植后不久发生感染性休克，导致移植物丢失，需要进行第二次移植。10例患者在移植后5至6个月出现胸腺生成证据。移植后12个月和24个月时，循环中幼稚CD4细胞计数中位数分别为44×10⁹/L（范围11 - 440×10⁹/L）和200×10⁹/L（范围5 - 310×10⁹/L），T细胞受体切除环分别为2,238/10⁶T细胞（范围320 - 8,807/10⁶T细胞）和4,184/10⁶T细胞（范围1,582 - 24,596/10⁶T细胞）。计数通常未达到年龄正常水平，但患者能够清除先前存在的感染及后续获得的感染。在中位时间49个月（范围22 - 80个月）时，8例患者停止预防性使用抗菌药物，5例患者停止免疫球蛋白替代治疗。11例接受移植组织活检的患者中有7例经组织学证实有胸腺生成，其中5例显示完全成熟直至哈索尔小体形成的终末阶段。还证实了自身免疫调节因子的表达。12例患者中有7例出现自身免疫并发症。2例患者早期短暂性自身免疫性溶血经治疗后缓解，未复发。另外5例患者持续存在自身免疫问题，包括甲状腺炎（3例）、溶血（1例）、血小板减少症（4例）和中性粒细胞减少症（1例）。
结论
本研究证实了先前的报道，即胸腺移植可使cDGS患者的T细胞重建，但幸存者中自身免疫并发症频繁。
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