1月10日,刊登在PNAS杂志上的一项研究"Indirect evidence that maternal microchimerism in cord blood mediates a graft-versus-leukemia effect in cord blood transplantation"说,用共同的父本血标记去匹配脐带血的受体和捐献者可能减少某些类型的白血病的复发率。
科研人员一直无法解释为什么脐带血——脐带血被认为在免疫上是不成熟的——被证明在攻击没有亲缘关系的受体的白血病细胞方面有效。Jon J. van Rood及其同事研究了来自纽约血液中心国家脐带血项目的信息,并报告说脐带血中母亲的免疫力可能阻止了白血病的复发。
在怀孕期间,女性常常变得对胎儿从父亲那里遗传的父本抗原具有免疫,制造出了进入胎儿血液循环的免疫系统细胞。这组作者提出了一种假说,即脐带血中的这些“敏化的”母亲细胞可能识别没有亲缘关系的移植受体的同样的遗传父本抗原(IPA)并且引发针对白血病细胞的强大的免疫应答。
这组科研人员观察到,与没有拥有和捐献者的血标记相同的受试者相比,患急性骨髓和淋巴白血病的受试者在接受了来自与捐助者的遗传父本抗原(IPA)匹配的脐带血之后白血病的复发率较低。这组作者说,这些发现可能有助于未来的癌症监测研究,而且可能整合到目前移植中心使用的用于帮助匹配脐带血捐献者和受体的搜索算法中。(生物谷Bioon.com)
doi:10.1073/pnas.1119541109
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Indirect evidence that maternal microchimerism in cord blood mediates a graft-versus-leukemia effect in cord blood transplantation
Jon J. van Rooda,1, Andromachi Scaradavoub, and Cladd E. Stevensb,2
During pregnancy women can develop B- and T-cell immunity against the inherited paternal antigens (IPAs) of the fetus, such as HLA, peptides of minor histocompatibilty antigens, and possibly onco-fetal antigens. The biological and pathological role of these pregnancy-induced immunological events is only understood in part. However, anti-IPA immunity in the mother persists for many decades after delivery and may reduce relapse in offspring with leukemia after HLA-haploidentical transplantation of maternal hematopoietic stem cells (HSC). We hypothesized that maternal anti-IPA immune elements cross the placenta and might confer a potent graft-versus-leukemia effect when cord blood (CB) is used in unrelated HSC transplantation. In a retrospective study of single-unit CB recipients with all grafts provided by the New York Blood Center, we show that patients with acute myeloid or lymphoblastic leukemia (n = 845) who shared one or more HLA-A, -B, or -DRB1 antigens with their CB donor's IPAs had a significant decrease in leukemic relapse posttransplantation [hazard ratio (HR) = 0.38, P < 0.001] compared with those that did not. Remarkably, relapse reduction in patients receiving CB with one HLA mismatch (HR = 0.15, P < 0.001) was not associated with an increased risk of severe acute graft-versus-host disease (HR = 1.43, P = 0.730). Our findings may explain the unexpected low relapse rate after CB transplantation, open new avenues in the study of leukemic relapse after HSC transplantation (possibly of malignancies in general), and have practical implications for CB unit selection.