Comprehensive mapping of immune perturbations associated with aplastic anemia

Abstract

Background

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.

Methods

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.

Results

Compared to HDs, peripheral blood from patients with AA exhibits a marked reduction in CD56^Dim 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^Bri cells and CD8⁺ T cell subsets, as well as between NK^Dim cells and CD4⁺ T cells, these results highlight the intricate interactions and correlations within the immune cell network in AA.

Conclusion

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.

Graphical Abstract