Proteomics analysis reveals alterations of NK cells in patients with severe aplastic anemia

Severe aplastic anemia (SAA) is a disease characterized by severe pancytopenia and hematopoietic failure of bone marrow. Natural killer (NK) cells are a class of large granular lymphocytes that perform killing and immunomodulatory functions. Our previous study demonstrated that NK cells played the “protective” role in SAA, which is weakened. However, the mechanism remains unclear.

Peripheral blood NK cells from SAA patients and normal controls were sorted and total proteins were extracted. Then, mass spectrometry was performed to screen differentially expressed proteins (DEPs).

Significant differences in the expression levels of 93 proteins were observed in NK cells of SAA patients compared with normal controls. Among them, 48 were upregulated proteins, including histone H1.2, histone H1.3, heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1), and interferon regulatory factor 1 (IRF‐1), and 45 were downregulated proteins, including actin‐related complex (ARP2/3), histone H3, histone H4, phosphoglycerate kinase 1 (PGK1), talin‐1. Gene Ontology (GO) function indicated that the DEPs most involved were vesicle‐mediated transport, innate immune response, and DNA binding. KEGG analysis showed 3 upregulated and 12 downregulated pathways, in which cell endocytosis and FC‐γ receptor‐mediated phagocytosis were most closely related to NK cell functions.

Our study is the first analysis of proteomic profile in NK cells in SAA and found many DEPs involving in dysfunction of NK cells, which provides potential targets for deeper research of inadequate immunomodulation.