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异基因干细胞移植后免疫重建和巨细胞病毒感染:体内 T 细胞耗竭的重要影响。

Immune reconstitution and cytomegalovirus infection after allogeneic stem cell transplantation: the important impact of in vivo T cell depletion.

机构信息

Medical Department III (Hematology, Oncology and Transfusion Medicine), Charité Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.

出版信息

Int J Hematol. 2010 Jun;91(5):877-85. doi: 10.1007/s12185-010-0597-6. Epub 2010 May 21.

Abstract

We analyzed cytomegalovirus (CMV) infection risk factors and immune reconstitution kinetics in 89 patients after allogeneic stem cell transplantation (allo-SCT). The use of alemtuzumab for in vivo T cell depletion (TCD) had, besides the donor/recipient CMV serostatus, the strongest influence on the CMV infection risk in univariate and multivariate analyses. In comparison to without use of in vivo TCD, the CMV infection risk [hazard ratio (HR)] was 4.82-fold after TCD with alemtuzumab, but only 1.40-fold after TCD with antithymocyte globulin (ATG). Alemtuzumab strongly depressed CD4(+) and CD8(+) T cell reconstitution, whereas ATG only delayed CD4(+) T cell reconstitution. Considering the reconstitution kinetics of CD4(+) and CD8(+) T cells, CMV-specific CD8(+) T cells, NK cells and the IgG concentration, only a low day +60 NK cell count (< or =161 versus >161/microl) was significantly associated with CMV infection development (HR 2.92, p = 0.034). CMV-specific CD8(+) T cells were detected in 57% of patients with a CMV-seropositive donor, but in none of the patients with a CMV-seronegative donor on day +30 (p = 0.01). Our data indicate that the type of in vivo TCD (alemtuzumab or ATG) differentially influences both the CMV infection risk and CD4(+)/CD8(+) T cell reconstitution kinetics in patients after allo-SCT.

摘要

我们分析了 89 例异基因造血干细胞移植(allo-SCT)后患者的巨细胞病毒(CMV)感染危险因素和免疫重建动力学。在单因素和多因素分析中,除了供体/受者 CMV 血清状态外,使用阿仑单抗进行体内 T 细胞耗竭(TCD)对 CMV 感染风险的影响最大。与未进行体内 TCD 相比,阿仑单抗 TCD 后的 CMV 感染风险(危险比[HR])为 4.82 倍,但抗胸腺细胞球蛋白(ATG)TCD 后的 HR 仅为 1.40 倍。阿仑单抗强烈抑制 CD4+和 CD8+T 细胞重建,而 ATG 仅延迟 CD4+T 细胞重建。考虑到 CD4+和 CD8+T 细胞、CMV 特异性 CD8+T 细胞、NK 细胞和 IgG 浓度的重建动力学,仅低的第+60 天 NK 细胞计数(<或=161 与>161/µl)与 CMV 感染发展显著相关(HR 2.92,p=0.034)。在 CMV 血清阳性供者的 57%患者中检测到 CMV 特异性 CD8+T 细胞,但在 CMV 血清阴性供者的患者中无一例在第+30 天检测到(p=0.01)。我们的数据表明,体内 TCD 的类型(阿仑单抗或 ATG)对 allo-SCT 后患者的 CMV 感染风险和 CD4+/CD8+T 细胞重建动力学有不同的影响。

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