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

Abstract

Severe aplastic anemia (SAA) is a disease characterized by severe pancytopenia and hematopoietic failure of bone marrow. The clinical features of SAA include severe infection, anemia, hemorrhage, and high mortality. 1 SAA is recognized as an immune disease, but the factors that cause the immune storm remain unclear. 2 Our previous study demonstrated that the number of myeloid dendritic cells (mDCs) in patients with SAA increases significantly and the expression level of transcription factor T-bet increases, which leads Abstract Introduction: 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.Methods: 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).Results: 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. Conclusion: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. K E Y W O R D Shistone, hnRNP A2/B1, NK cells, PGK1, Severe aplastic anemia

Levamisole Suppresses CD4+ T-Cell Proliferation and Antigen-Presenting Cell Activation in Aplastic Anemia by Regulating the JAK/STAT and TLR Signaling Pathways

“…To explore the underlying molecular mechanisms and potential cellular targets of LMS, we focused on the TLR and JAK/STAT signaling pathways by the virtual docking assay and transcriptional analysis. The TLR signaling pathway participates in the innate immune response and may induce the pathogenesis of AA by triggering adaptive immunity (35,36). Young et al (37) found that TLRs presented increased mRNA expression in the CD4 + T cells and also had a similar response on the CD8 + T cells from AA patients.…”

The Actin Regulators Involved in the Function and Related Diseases of Lymphocytes

“…Finally, a recent mass spectrometry study of NK cell protein expression in severe aplastic anemia (SAA) patients found that the Arp2/3 complex is downregulated in NK cells ( 315 ), suggesting a role in the disease-protective function of NK cells in SAA.…”

Single‐cell transcriptomic analysis of PB and BM NK cells from severe aplastic anaemia patients

“…Our pilot research indicated that NK cell number and function were abnormal in SAA patients, 1 and we also identified several proteins associated with NK cell dysfunction by proteomic analysis. 2 To further explore the subgroups of NK cells that may be implicated in the pathogenesis of SAA and find the differences between bone marrow NK cells (BM‐NK) and peripheral blood NK cells (PB‐NK), we conducted single‐cell RNA sequencing (scRNA‐seq) on BM‐NK and PB‐NK of SAA patients and healthy volunteers (HC).…”

“…cell dysfunction by proteomic analysis. 2 To further explore the subgroups of NK cells that may be implicated in the pathogenesis of SAA and find the differences between bone marrow NK cells (BM-NK) and peripheral blood NK cells (PB-NK), we conducted single-cell RNA sequencing (scRNA-seq) on BM-NK and PB-NK of SAA patients and healthy volunteers (HC). In keeping with our preceding studies, 1 the percentage of BM-NK was higher than that PB-NK in both HC and SAA, and the percentage of PB-NK and BM-NK were both markedly lower in the SAA than in the HC (Figure S1).…”