Department of Hematology, Guangzhou First People's Hospital, Guangzhou, 510180, China.
Center for Medical Research On Innovation and Translation, Guangzhou First People's Hospital, Guangzhou, 510180, China.
Cell Biol Toxicol. 2024 Sep 13;40(1):75. doi: 10.1007/s10565-024-09914-0.
Aplastic anemia (AA) is an immune-mediated syndrome characterized by bone marrow failure. Therefore, comprehending the cellular profile and cell interactions in affected patients is crucial.
Human peripheral blood mononuclear cells (PBMCs) were collected from both healthy donors (HDs) and AA patients, and analyzed using multicolor flow cytometry. Utilizing the FlowSOM and t-SNE dimensionality reduction technique, we systematically explored and visualized the major immune cell alterations in AA. This analysis provided a foundation to further investigate the subtypes of cells exhibiting significant changes.
Compared to HDs, peripheral blood from patients with AA exhibits a marked reduction in CD56 natural killer (NK) cells, which also show diminished functionality. Conversely, an increase in NK-like CD56 monocytes, which possess compromised functionality. Along with a significant reduction in myeloid-derived suppressor cells (MDSCs), which show recovery post-treatment. Additionally, MDSCs serve as effective clinical markers for distinguishing between acquired aplastic anemia (AAA) and congenital aplastic anemia (CAA). Our comprehensive analysis of correlations among distinct immune cell types revealed significant associations between NK cells and CD8 T cell subsets, as well as between NK cells and CD4 T cells, these results highlight the intricate interactions and correlations within the immune cell network in AA.
Our study systematically elucidates the pronounced immune dysregulation in patients with AA. The detailed mapping of the immune landscape not only provides crucial insights for basic research but also holds promise for enhancing the accuracy of diagnoses and the effectiveness of timely therapeutic interventions in clinical practice. Consequently, this could potentially reduce the high mortality rate associated with AA.
再生障碍性贫血（AA）是一种免疫介导的综合征，其特征是骨髓衰竭。因此，了解受影响患者的细胞特征和细胞相互作用至关重要。
从健康供体（HD）和 AA 患者中收集人外周血单核细胞（PBMC），并使用多色流式细胞术进行分析。我们利用 FlowSOM 和 t-SNE 降维技术，系统地探索和可视化 AA 中主要免疫细胞的改变。该分析为进一步研究表现出显著变化的细胞亚型提供了基础。
与 HD 相比，AA 患者的外周血中 CD56 自然杀伤（NK）细胞明显减少，其功能也降低。相反，NK 样 CD56 单核细胞增加，但其功能受损。髓系来源抑制细胞（MDSC）显著减少，治疗后恢复。此外，MDSC 可作为区分获得性再生障碍性贫血（AAA）和先天性再生障碍性贫血（CAA）的有效临床标志物。我们对不同免疫细胞类型之间的相关性进行全面分析，发现 NK 细胞与 CD8 T 细胞亚群之间以及 NK 细胞与 CD4 T 细胞之间存在显著关联，这些结果突出了 AA 中免疫细胞网络内的复杂相互作用和关联。
我们的研究系统地阐明了 AA 患者明显的免疫失调。免疫景观的详细描绘不仅为基础研究提供了重要的见解，而且有望提高临床实践中诊断的准确性和及时治疗干预的效果。因此，这可能降低与 AA 相关的高死亡率。
