Comprehensive mapping of immune perturbations associated with aplastic anemia

Background Acquired aplastic anemia (AA) is an immune-mediated syndrome resulting in bone marrow failure. Therefore, comprehending the profile and cell interactions in affected patients is crucial. Methods Human peripheral blood mononuclear cells (PBMCs) were collected from both healthy donors (HD) and AA patients, and analyzed using multicolor flow cytometry. Utilizing FlowSOM, we explored and visualized the immunophenotypic and metabolic characteristics of AA. Results Patients with AA show increased CD56 ⁺ monocytes with NK characteristics and activated cytotoxic T cells in peripheral blood compared to HD. Conversely, less functional CD56 ^dim NK cells, regulatory T cells and myeloid-derived suppressor cells (MDSCs) decrease in AA. Additionally, MDSCs demonstrate post-treatment recovery and can serve as clinical indicators to distinguish between acquired aplastic anemia (AA) and congenital aplastic anemia (CAA). We assessed correlations among 29 immune cell types and found that a significant increase in memory B cells, eosinophils, and NK bright cells, along with a marked decrease in NK dim and non-classic monocytes, indicates a discernible interplay and correlation among these immune cell populations. Conclusion Our study results demonstrate significant immune dysregulation in patients with AA. Thus, CD56 ⁺ monocytes with NK characteristics, activated cytotoxic T cells, less functional CD56 ^dim NK cells, Treg cells, and MDSCs may play crucial roles in the onset and progression of AA, serving as potential diagnostic biomarkers. These findings are expected to facilitate accurate diagnosis and timely treatment, thereby reducing the high mortality rate.