OBJECTIVE: To determine the cytotoxicity of natural killer (NK) cells and the level of differentiation of hematopoietic stem cells (HSCs) into NK cells in systemic lupus erythematosus (SLE). METHODS: Patients with SLE (n=108), rheumatoid arthritis (RA; n=90), Behçet's disease (n=39), or ankylosing spondylitis (n=41) and healthy control subjects (n=173) were enrolled in the study. NK cell levels, NK cell cytotoxicities, and lymphokine-activated killer (LAK) activities against K562 cells were measured by flow cytometry. Gene expression was assessed by reverse transcription-polymerase chain reaction. NK cells were differentiated from peripheral blood and bone marrow HSCs in vitro. RESULTS: Percentages and absolute numbers of NK cells, cytotoxicities, and LAK activities were significantly lower in the peripheral blood of SLE and RA patients than in that of healthy controls. In particular, this NK cell deficiency was more prominent in patients with lupus nephritis and those with thrombocytopenia. Notably, purified NK cells derived from SLE patients, but not RA patients, were found to have lower cytotoxicities and LAK activities than those from healthy controls. This defect of NK cells in SLE patients was found to be related to lower numbers of NK precursors and to the down-regulation of perforin and granzyme in NK cells. The proliferative capacity of HSCs, the percentages of NK cells differentiated from HSCs, and NK cell cytotoxicities were significantly lower in SLE patients. CONCLUSION: In SLE patients, circulating levels of NK cells were diminished and their cytotoxicities were impaired. Furthermore, the differentiation of HSCs into NK cells was found to be defective. These abnormalities possibly contribute to immune system dysregulation in SLE.
OBJECTIVE: To determine the cytotoxicity of natural killer (NK) cells and the level of differentiation of hematopoietic stem cells (HSCs) into NK cells in systemic lupus erythematosus (SLE). METHODS:Patients with SLE (n=108), rheumatoid arthritis (RA; n=90), Behçet's disease (n=39), or ankylosing spondylitis (n=41) and healthy control subjects (n=173) were enrolled in the study. NK cell levels, NK cell cytotoxicities, and lymphokine-activated killer (LAK) activities against K562 cells were measured by flow cytometry. Gene expression was assessed by reverse transcription-polymerase chain reaction. NK cells were differentiated from peripheral blood and bone marrow HSCs in vitro. RESULTS: Percentages and absolute numbers of NK cells, cytotoxicities, and LAK activities were significantly lower in the peripheral blood of SLE and RApatients than in that of healthy controls. In particular, this NK cell deficiency was more prominent in patients with lupus nephritis and those with thrombocytopenia. Notably, purified NK cells derived from SLEpatients, but not RApatients, were found to have lower cytotoxicities and LAK activities than those from healthy controls. This defect of NK cells in SLEpatients was found to be related to lower numbers of NK precursors and to the down-regulation of perforin and granzyme in NK cells. The proliferative capacity of HSCs, the percentages of NK cells differentiated from HSCs, and NK cell cytotoxicities were significantly lower in SLEpatients. CONCLUSION: In SLEpatients, circulating levels of NK cells were diminished and their cytotoxicities were impaired. Furthermore, the differentiation of HSCs into NK cells was found to be defective. These abnormalities possibly contribute to immune system dysregulation in SLE.
Authors: Guillermo Carvajal Alegria; Pierre Gazeau; Sophie Hillion; Claire I Daïen; Divi Y K Cornec Journal: Clin Rev Allergy Immunol Date: 2017-10 Impact factor: 8.667
Authors: Roberto Spada; José M Rojas; Sonia Pérez-Yagüe; Vladimir Mulens; Pablo Cannata-Ortiz; Rafael Bragado; Domingo F Barber Journal: J Leukoc Biol Date: 2015-01-12 Impact factor: 4.962
Authors: M Pérez-Ferro; F I Romero-Bueno; C Serrano Del Castillo; I Mahillo; A Alvear; R Largo; G Herrero-Beaumont; O Sánchez-Pernaute Journal: Clin Exp Immunol Date: 2019-02-27 Impact factor: 4.330