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Rabbit antithymocyte globulin (Thymoglobulin®) impairs the thymic output of both conventional and regulatory CD4+ T cells after allogeneic hematopoietic stem cell transplantation in adult patients

机译：成年患者异基因造血干细胞移植后兔抗胸腺细胞球蛋白（Thymoglobulin®）损害常规和调节性CD4 + T细胞的胸腺输出

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Rabbit antithymocyte globulin-Genzyme™ is used to prevent graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Common disadvantages of treatment are infectious complications. The effects of rabbit antithymocyte globulin-Genzyme™ on thymic function have not been well-studied. Multicolor flow cytometry was used to analyze the kinetics of conventional and regulatory T cells in adult patients treated (n=12) or not treated (n=8) with rabbit antithymocyte globulin-Genzyme™ during the first 6 months after allogeneic hematopoietic stem cell transplantation. Patients treated with rabbit antithymocyte globulin-Genzyme™ had almost undetectable levels of recent thymic emigrants (CD45RA⁺CD31⁺) of both conventional and regulatory CD4T cells throughout the 6 months after allogeneic hematopoietic stem cell transplantation whereas CD4⁺CD45RA-memory T cells were less affected, but their levels were also significantly lower than in patients not treated with rabbit antithymocyte globulin-Genzyme™. In vitro, rabbit antithymocyte globulin-Genzyme™ induced apoptosis and cytolysis of human thymocytes, and its cytotoxic effects were greater than those of rabbit antithymocyte globulin-Fresenius™. Rabbit antithymocyte globulin-Genzyme™ in combination with a conditioning regimen strongly impairs thymic recovery of both conventional and regulatory CD4⁺ T cells. The sustained depletion of conventional and regulatory CD4⁺T cells carries a high risk of both infections and graft-versus-host disease. Our data indicate that patients treated with rabbit antithymocyte globulin-Genzyme™ could benefit from thymus-protective therapies and that trials comparing this product with other rabbit antithymocyte globulin preparations or lymphocyte-depleting compounds would be informative.

机译：兔抗胸腺细胞球蛋白-Genzyme™用于预防异基因造血干细胞移植后的移植物抗宿主病。治疗的共同缺点是感染性并发症。尚未充分研究兔抗胸腺细胞球蛋白-Genzyme™对胸腺功能的影响。多色流式细胞术用于分析同种异体造血干细胞移植后头6个月内用兔抗胸腺细胞球蛋白Genzyme™治疗（n = 12）或未治疗（n = 8）的成年患者常规和调节性T细胞的动力学。在异基因治疗后的6个月中，用常规抗调节性CD4T细胞和常规调节性CD4T细胞治疗的兔抗胸腺细胞球蛋白Genzyme™患者的胸腺移出物（CD45RA ^{+ CD31 ^{+ ）的水平几乎未检测到造血干细胞移植，而CD4 ^{+ CD45RA记忆T细胞受到的影响较小，但其水平也显着低于未用兔抗胸腺细胞球蛋白Genzyme™治疗的患者。在体外，兔抗胸腺细胞球蛋白-Genzyme™诱导人胸腺细胞凋亡和细胞溶解，其细胞毒性作用大于兔抗胸腺细胞球蛋白-Fresenius™。兔抗胸腺细胞球蛋白-Genzyme™与条件疗法相结合会强烈损害常规CD4 ^{+ T细胞的胸腺恢复。常规和调节性CD4 ^{+ T细胞的持续耗竭具有感染和移植物抗宿主病的高风险。我们的数据表明，用兔抗胸腺细胞球蛋白-Genzyme™治疗的患者可以受益于胸腺保护疗法，并且将该产品与其他兔抗胸腺细胞球蛋白制剂或消耗淋巴细胞的化合物进行比较的试验将是有益的。}}}}}

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期刊名称 Haematologica
作者
Il-Kang Na; Friedrich Wittenbecher; Mikalai Dziubianau; Anne Herholz; Angela Mensen; Désirée Kunkel; Olga Blau; Igor Blau; Eckhard Thiel; Lutz Uharek; Carmen Scheibenbogen; Kathrin Rieger; Andreas Thiel;
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年(卷),期 2013(98),1
年度 2013
页码 23–30
总页数 8
原文格式 PDF
正文语种
中图分类血液学检验;
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专利

1. Reply to: Transient Grades Three to Four Acute Hepatitis Is a Common Complication of Rabbit Antithymocyte Globulin (Thymoglobulin) Administered before Allogeneic Stem Cell Transplantation [J] . Remberger Mats, Mattsson Jonas Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation . 2015,第6期

机译：回复：暂时性三至四级急性肝炎是异体干细胞移植前施用兔抗胸腺细胞球蛋白（胸腺球蛋白）的常见并发症
2. Reply to: Transient Grades Three to Four Acute Hepatitis Is a Common Complication of Rabbit Antithymocyte Globulin (Thymoglobulin) Administered before Allogeneic Stem Cell Transplantation [J] . Remberger Mats, Mattsson Jonas Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation . 2015,第6期

机译：回复：三到四级急性丙型肝炎的瞬时等级是在同种异体干细胞移植前施用的兔antithymocyte球蛋白（胸腺杂菌素）的常见并发症
3. A Chemotherapy-Only Regimen of Busulfan, Melphalan, and Fludarabine, and Rabbit Antithymocyte Globulin Followed by Allogeneic T-Cell Depleted Hematopoietic Stem Cell Transplantations for the Treatment of Myeloid Malignancies [J] . Barbara Spitzer, Ann A. Jakubowski, Esperanza B. Papadopoulos, Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation . 2017,第12期

机译：仅由Busulfan，Melphalan和Fludarabine的化疗方案，以及兔Antithymocyte球蛋白，然后是同种异体T细胞耗尽的造血干细胞移植治疗骨髓性恶性肿瘤
4. THE EFFECT OF INHIBITORY KILLER-CELL IG-LIKE RECEPTOR (IKIR) MATCHING IN ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION (HCT) [C] . David Senitzer, Joel Y. Sun, Arisa Oki, Clinical Histocompatibility Workshop. . 2009

机译：同种异体造血细胞移植（HCT）中抑制杀伤细胞IG样受体（IKIR）匹配的影响
5. Donor selection for patients undergoing allogeneic hematopoietic stem cell transplantation: Assessment of the priorities of Canadian hematopoietic stem cell transplant physicians. [D] . Tay, Jason. 2009

机译：接受同种异体造血干细胞移植的患者的供体选择：加拿大造血干细胞移植医生的优先事项评估。
6. Lower Dose of Antithymocyte Globulin (ATG) does not increase Graft-vs-Host Disease (GVHD) in Patients Undergoing Reduced-Intensity Conditioning (RIC) Allogeneic Hematopoietic Stem Cell Transplant (allo HSCT) [O] . Galena Salem, Amy S. Ruppert, Patrick Elder, -1

机译：接受低强度调节（RIC）同种异体造血干细胞移植（allo HSCT）的患者较低剂量的抗胸腺细胞球蛋白（ATG）不会增加Graft-vs-宿主疾病（GVHD）
7. Rabbit antithymocyte globulin (Thymoglobulin(R)) impairs the thymic output of both conventional and regulatory CD4+ T cells after allogeneic hematopoietic stem cell transplantation in adult patients [O] . I.-K. Na, F. Wittenbecher, M. Dziubianau, 2012

机译：兔Antithymocyte球蛋白（胸腺球蛋白（R））在成人患者中同种异体造血干细胞移植后损害常规和调节CD4 + T细胞的胸腺输出

Rabbit antithymocyte globulin (Thymoglobulin®) impairs the thymic output of both conventional and regulatory CD4+ T cells after allogeneic hematopoietic stem cell transplantation in adult patients

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