NK cells dysfunction in systemic lupus erythematosus: relation to disease activity (original) (raw)
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Arthritis & Rheumatism, 2011
Methods. A total of 94 patients with SLE (91 women and 3 men) were compared with 26 healthy controls. Active SLE was defined by an SLE Disease Activity Index score >4. Immunologic tests were performed using nonactivated and/or interleukin-2 (IL-2)activated peripheral blood mononuclear cells. NK cell phenotype was determined by flow cytometry. NK cell natural cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) were determined by 51 Cr release and CD107a degranulation experiments. Intracellular interferon-␥ (IFN␥) production by NK cells was evaluated after overnight stimulation with IL-12 and IL-18. IFN␣ levels were assessed using an antiviral cytopathic bioassay.
Reumatologia/Rheumatology
Introduction: Systemic lupus erythematosus (SLE) patients have decreased natural killer (NK) cell counts. The decrease in the number of NK cells has implications for a decrease in the function of NK cells which can affect the progression of SLE disease. The study aim was to determine profiles of CD3-CD56 bright and CD3-CD56 dim NK cells in SLE patients and their relation to disease activity. Material and methods: This study included 36 patients of SLE who fulfilled the ACR 1997/SLICC 2012 criteria, women aged 18-49 years. Disease activity was assessed by the Mex-SLEDAI. Peripheral blood samples from SLE patients were analyzed by flow cytometry to evaluate NK cell subsets, according to differential expression of the main subset of NK cells, which is CD3-CD56 bright and CD3-CD56 dim. Results: The mean percentage of regulatory NK cell count (CD3-CD56 bright) in active SLE patients was significantly lower (p = 0.000) than in inactive SLE patients. The mean percentage of cytotoxic NK cell count (CD3-CD56 dim) in active SLE patients was significantly (p = 0.000) higher than in inactive SLE patients. A correlation was observed between two subsets of NK cells with disease activity (p = 0.00). The percentage of CD3-CD56 bright NK cells was negatively correlated with disease activity (r =-0.766), whereas the percentage of CD3-CD56 dim NK cells positively correlated with disease activity (r = 0.761). Conclusions: There is a difference in the mean percentage of the number of NK cells (CD3-CD56+) in both a subset of regulatory NK cells (CD3-CD56 bright) and cytotoxic NK cells (CD3-CD56 dim) in active and inactive SLE patients and it is closely related to SLE disease activity.
Clinical & Experimental Immunology
Summary Natural killer (NK) cells participate in the regulation of the immune response. However, the immunomodulatory function of NK cells in systemic lupus erythematosus (SLE) is not well understood. The aim of this study was to evaluate the regulatory function of NK cells in SLE patients and to identify the NK cells involved in the pathogenesis of this complex disease. We analysed the expression of NK receptors and co-stimulatory molecules in peripheral NK cells (CD3−CD56+) from SLE patients, as well as the numbers of human leucocyte antigen D-related (HLA-DR)/CD11c+ NK cells. In addition, NK cell regulatory function was assessed by the detection of NK cell-mediated dendritic cell (DC) lysis. We found that SLE patients showed increased numbers of immunoglobulin-like transcript 2 (ILT2)+, CD86+ and CD134+ NK cells. Furthermore, NK cells from SLE patients induced higher levels of DC lysis. We were able to identify a new subset of NK cells co-expressing CD11c and HLA-DR. These atypic...
Natural Killer Cell Count in Systemic Lupus Erythematosus Patients: A Flow Cytometry-Based Study
Cureus, 2023
Background Natural killer cells (NK cells) are important mediators of innate immune regulation and literature has shown that they have a role in shaping the adaptive immune system. Objective The present study was undertaken to analyze the NK cell count in systemic lupus erythematosus (SLE) patients as compared to that of controls. Materials and methods Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA-SLEDAI) score was assessed in 32 SLE cases. CD3(-) cells were identified as NK cells on flow cytometry, and then their subsets CD56(+) and CD16(+) cells were identified compared to 30 healthy controls. Receiver Operating Characteristic (ROC) curve analysis was performed on NK cells to attempt to determine a cutoff point. Results The CD3(-) NK cells, including the percentages of CD56(+) and CD16(+), were significantly (p<0.001) reduced in SLE patients (12.35%, and 18.7%) as compared to controls (24.67%, and 46.6%). On ROC curve analysis, cutoff values <481/cumm with sensitivity of 86.7% and specificity of 84.4% for CD3(-) NK cells (p<0.001), <23% with 60% sensitivity and 75% specificity for CD56(+) NK cells (p<0.001), and <29% with sensitivity of 70% and specificity of 87.5% for CD16(+) NK cells (p<0.001) were noted. Subsets of NK cells showed no association with the clinicopathological parameters like age, sex, disease activity, anti-nuclear antibodies (ANA), dsDNA, absolute lymphocyte count, and renal involvement. Conclusion NK cells, and their subpopulations of CD56(+) and CD16(+) cells, are decreased in patients with SLE as compared to controls.
PLOS ONE, 2017
Natural killer (NK) cells may play an important role in the pathogenesis of SLE. Interleukin (IL)-15, an NK-enhancing cytokine, is over-expressed in SLE patients. In the present study, we examined the effect of IL-15 on NK cytotoxicity of SLE patients, and the expression of various activating and inhibitory NK receptors on NK cells from SLE patients in relation to disease activity. We also sought to determine how IL-15 would affect the NK receptor expression on NK cells from SLE patients. PBMCs were collected from 88 SLE patients with inactive disease activity (SLEDAI score<6) and active disease activity (SLEDAI score!6), 26 age-matched healthy adults were used as controls. PBMC were incubated in the presence or absence of IL-15 (10ng/ml) for eighteen hours. CD3-CD56 + lymphoctes were gated using flow cytometry and further divided into CD56 dim and CD56 bright subsets according to the MFI of CD56. We observed that 1. Serum IL-15 was elevated in SLE patients, and higher in active disease than in inactive disease; 2. NK cytotoxicity of SLE patients was deficient compared to controls and showed an impaired response to IL-15 compared to controls; 3. CD69, CD94, NKG2A, NKp30, and CD158b on NK cells from SLE patients were higher than controls, and could be further enhanced by IL-15; 4. NKp46 expression from SLE patients was higher than controls, but down-regulated by IL-15; 5.Deficient NKG2D and NKAT-2 expression were found on NK cells from SLE patients, which were enhanced by IL-15; 6. A unique NKp46subset and CD158b + subsets were observed in NK cells from SLE patients but not controls. 7. Unlike controls, CD158k on NK cells from SLE patients failed to respond to IL-15. Taken together, we demonstrated the aberrant NCR and iNKR expression on NK cells and their distinct response to IL-15 in SLE patients. As IL-15 predominantly aggravates the aberrant NKR expression found in SLE, IL-15 antagonist may have therapeutic benefits in SLE patients.
Arthritis and Rheumatism, 1985
Interferon (IFN) production and response are impaired in a high percentage of systemic lupus erythematosus (SLE) patients. In addition, elevated serum levels of a-IFN or anti-a-IFN antibodies are present in some SLE patients. This study examined the relationship of circulating IFN and anti-IFN antibodies to the impairment of natural killer (NK) cell function in SLE. All 15 SLE patients studied had measurable circulating a-IFN, while the normal controls had minimal serum IFN. Neither patient nor control sera contained any detectable anti-a-IFN activity. However, most of the SLE patients demonstrated defects in NK cell function. Because these defects in NK cell function appeared to be associated with circulating IFN, but not anti-IFN, antibodies, the effect of prolonged in vitro IFN exposure on NK cell function of peripheral blood qpnonuclear cells was determined. It was found that prolonged exposure to IFN induced both an apparent defect in IFN response and a definite impairment of baseline NK cell function. These results suggest that prolonged elevation of circulating a-IFN levels could be responsible, in part, for the defects in natural cytotoxicity present in SLE. Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterized by multi-From the
Expansion of an atypical NK cell subset in mouse models of systemic lupus erythematosus
Journal of immunology (Baltimore, Md. : 1950), 2015
Chronic inflammatory conditions, such as in autoimmune disease, can disturb immune cell homeostasis and induce the expansion of normally rare cell populations. In our analysis of various murine models of lupus, we detect increased frequency of an uncommon subset identified as NK1.1(+)CD11c(+)CD122(+)MHC class II(+). These cells share characteristics with the NK cell lineage and with cells previously described as IFN-producing killer dendritic cells: 1) they depend on IL-15 and express E4BP4; 2) they are cytotoxic and produce type I and type II IFN upon activation; and 3) they are efficient APCs both through MHC class II expression and in cross-presentation to CD8s. These atypical NK cells are responsive to TLR stimulation and thus are most abundant in mice with high copy number of the Tlr7 gene. They are highly proliferative as assessed by in vivo BrdU incorporation. In adoptive transfer experiments they persist in high numbers for months and maintain their surface marker profile, i...
Journal of immunology (Baltimore, Md. : 1950), 2018
Cytotoxic function and cytokine profile of NK cells are compromised in patients with systemic lupus erythematosus (SLE). CD3ζ, an important molecule for NK cell activation, is downregulated in SLE T cells and contributes to their altered function. However, little is known about the role of CD3ζ in SLE NK cells. We studied CD3ζ levels and its contribution to cytotoxic, degranulation, and cytokine production capacity of NK cells from patients with SLE. Furthermore, we studied the human NK cell line, NKL, in which manipulation of CD3ζ levels was achieved using small interfering RNA and NK cells from mice deficient in CD3ζ. We found reduced CD3ζ expression in NK cells from SLE patients independent of disease activity. Downregulation of CD3ζ expression in NK cells is mediated, at least in part, by Caspase 3, the activity of which is higher in NK cells from patients with SLE compared with NK cells from healthy donors. CD3ζ levels correlated inversely with natural cytotoxicity and the perc...
British Journal of Dermatology, 1987
Peripheral blood mononuclear cells from 63 patients with systemic scleroderma, including incipient or prodromal acrosclerosis, and from 20 healthy individuals were tested for natural killer (NK) cell activity and antibody-dependent cell cytotoxicity in a 4 h 5'Cr release assay using K562 and Lt2io cell lines respectively. In patients with systemic scleroderma natural killer cell activity was significantly decreased compared with the controls. NK cell activity was markedly lowered in patients with diffuse scleroderma and in transitional form acrosclerosis-diffuse scleroderma, and was normal in cases of acrosclerosis and/or CREST syndrome and in cases of prodromal or incipient scleroderma. Antibody-dependent cell cytotoxicity of mononuclear cells from the systemic scleroderma patients was within the normal range. The lowered natural killer cell activity correlated with the severity of systemic scleroderma, in terms of the extent of skin and organ involvement.