Role of NK cells in immune escape in patients with classical paroxysmal nocturnal hemoglobinuria

Abstract Abstract Background: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder. Immune escape is crucial in PNH, but the role of natural killer (NK) cells remains unclear. Our previous studies revealed that NK cells participate in the immune escape of PNH. Thus, this study aimed to investigate the functional status of NK cells in PNH and their role in immune escape. Methods: Our previous studies have analyzed CD59+and CD59-bone marrow mononuclear cells (BMMNCs) using single-cell RNA sequencing(scRNA-seq) and revealed that activated normal NK cells participate in the immune escape process of PNH. We further analyzed NK cells using scRNA-seq and flow cytometry were performed to assess NK cell in the bone marrow and peripheral blood of 26 patients with PNH and 27 HCs. Results: The scRNA-seq results showed impaired function in CD59-NK cells, whereas CD59+ NK cells showed minimal change. The proportion of active and adaptive NK cells increased in CD59+NK cells, and the cytotoxic function and cytokine secretion were significantly stronger than those in CD59- active NK cells and controls. The proportion of CD56brightNK and terminal NK cells was increased in CD59- NK cells, but chemokine expression was decreased. The proportion of mature NK decreased in both CD59+ and CD59- groups. These results suggest that CD59+NK cells contribute to immune escape, while CD59−NK cells exhibit functional defects. Furthermore, NK cell alterations correlated with CD8+T-cell proportions and disease severity. Conclusions: In summary, this study revealed that activated normal NK cells are involved in immune escape in PNH, providing novel insights into NK cell dysfunction in PNH and highlighting their potential role in immune escape. Keywords: paroxysmal nocturnal hemoglobinuria, natural killer cells, immune escape