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10.1016/j.ijid.2021.02.019

http://scihub22266oqcxt.onion/10.1016/j.ijid.2021.02.019
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33578018!7872850!33578018
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suck abstract from ncbi


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pmid33578018      Int+J+Infect+Dis 2021 ; 105 (ä): 49-53
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  • The unbalanced p53/SIRT1 axis may impact lymphocyte homeostasis in COVID-19 patients #MMPMID33578018
  • Bordoni V; Tartaglia E; Sacchi A; Fimia GM; Cimini E; Casetti R; Notari S; Grassi G; Marchioni L; Bibas M; Capobianchi MR; Locatelli F; Maeurer M; Zumla A; Antinori A; Nicastri E; Ippolito G; Agrati C
  • Int J Infect Dis 2021[Apr]; 105 (ä): 49-53 PMID33578018show ga
  • BACKGROUND/OBJECTIVES: A dysregulated inflammatory profile plays an important role in coronavirus disease-2019 (COVID-19) pathogenesis. Moreover, the depletion of lymphocytes is typically associated with an unfavourable disease course. We studied the role and impact of p53 and deacetylase Sirtuin 1 (SIRT1) on lymph-monocyte homeostasis and their possible effect on T and B cell signalling. METHODS: Gene expression analysis and flow cytometry were performed on peripheral blood mononuclear cells (PBMC) of 35 COVID-19 patients and 10 healthy donors (HD). Inflammatory cytokines, the frequency of Annexin+ cells among CD3+ T cells and CD19+ B cell subsets were quantified. RESULTS: PBMC from COVID-19 patients had a higher p53 expression, and higher concentrations of plasma proinflammatory cytokines (IL1beta, TNF-alpha, IL8, and IL6) than HD. Deacetylase Sirtuin 1 (SIRT1) expression was significantly decreased in COVID-19 patients and was negatively correlated with p53 (p = 0.003 and r = -0.48). A lower expression of IL-7R and B Cell linker (BLNK), key genes for lymphocyte homeostasis and function, was observed in COVID-19 than in HD. The reduction of IgK and IgL chains was seen in lymphopenic COVID-19 patients. A significant increase in both apoptotic B and T cells were observed. Inflammatory cytokines correlated positively with p53 (IL-1beta: r = 0.5 and p = 0.05; IL-8: r = 0.5 and p = 0.05) and negatively with SIRT1 (IL1-beta: r = -0.5 and p = 0.04; TNF-alpha: r = -0.4 and p = 0.04). CONCLUSIONS: Collectively, our data indicate that the inflammatory environment, the dysregulated p53/SIRT1 axis and low expression of IL7R and BLNK may impact cell survival, B cell signalling and antibody production in COVID-19 patients. Further studies are required to define the functional impact of low BLNK/IL7R expression during severe acute respiratory syndrome coronavirus-2 infection.
  • |*Homeostasis[MESH]
  • |*SARS-CoV-2[MESH]
  • |Aged[MESH]
  • |COVID-19/*immunology[MESH]
  • |Cytokines/blood[MESH]
  • |Female[MESH]
  • |Humans[MESH]
  • |Lymphocytes/*immunology[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Sirtuin 1/*physiology[MESH]


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