再生障碍性贫血（再障）是严重的骨髓衰竭性疾病，骨髓区域免疫紊乱不但与发病密切相关，也严重影响包括造血干细胞移植在内的治疗效果。我们过去的系列研究发现接受造血干细胞移植前再障患者体内高水平HLA抗体（anti-HLA）影响造血干细胞的植入，是移植相关死亡的高危因素；但是这些改变如何影响再障骨髓区域免疫微环境，使自身或植入的造血干细胞失去骨髓微环境的免疫豁免保护，导致再障发生或植入失败的机制亟待进一步研究。本项目将在前期发现的基础上，结合新近建立的高级骨髓成像等技术，系统分析anti-HLA+再障骨髓微环境中区域免疫特征；深入研究anti-HLA对造血干细胞免疫豁免微环境在细胞和因子组成上的破坏；初步探索再障骨髓区域免疫稳态重建的对策；为合理使用免疫治疗和造血干细胞移植治疗提供理论和实验依据。

Acquired aplastic anemia is a bone marrow failure disease associated with immune disorders in bone marrow microenvironment. We recently reported that pre-existing anti-HLA antibodies negatively affect the outcome of hematopoietic stem cell transplantation in pediatric aplastic anemia patients. However, the change in bone marrow niche caused by anti-HLA antibodies and the pathogenesis and mechanism of graft failure remains to be investigated. In the proposed project we will study the regional immune characteristics in bone marrow of aplastic anemia, investigate the destruction of immune-privilege niche made by anti-HLA antibodies including proportion and location of cells and cytokine disorders, explore the approach to reestablish homeostasis of bone marrow niche, which resulting in new knowledge and evidence of treatment for aplastic anemia.