scholarly journals CD3-(CD56 or 16)+ natural killer cell distribution in blood from healthy adults and patients with ANCA-associated vasculitis

2020 ◽  
Author(s):  
Wolfgang Merkt ◽  
Ulrich Salzer ◽  
Jens Thiel ◽  
Ilona Jandova ◽  
Raoul Bergner ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Granulomatosis With Polyangiitis ◽  
Nk Cell ◽  
Inflammatory Diseases ◽  
Clinical Care ◽  
Healthy Adults ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Cell Counts ◽  
Anca Associated Vasculitis

Abstract BackgroundCytotoxic Natural Killer (NK) cells are an important target of new drugs entering the clinics, including checkpoint inhibitors and cell-depleting therapeutic antibodies. Still, basic blood NK cell parameters are poorly defined in healthy adults and in chronic inflammatory diseases like ANCA-associated vasculitis (AAV) which may alter the distribution of lymphocytes. The aims of this study were 1) to establish reference values of NK cell counts and percentages in healthy adults; 2) to describe these parameters in AAV; and 3) to investigate whether NK cell counts and percentages may be used as activity biomarker in the care of AAV patients, as suggested by a preceding study.MethodsCD3-(CD56 or 16)+ NK cell counts and percentages were determined in 120 healthy adults. Lymphocyte subset data from two German vasculitis centers were retrospectively analyzed (in total 407 measurements, including 201/49/157 measurements from 64/16/39 patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), respectively).ResultsCD3-(CD56 or 16)+ NK cell counts and percentages in healthy adults were highly variable, not Gaussian distributed and independent of age and sex. NK cell percentages ranged from 1.9 to 37.9% of lymphocytes, and were significantly more dispersed in AAV (0.3 to 57.6%). We further found that NK cell counts and percentages were different between AAV entities. However, during active disease, NK cell counts were consistently low in each AAV entity compared to healthy donors. NK cells were especially low in inactive EGPA. In 18% of EGPA patients we observed percentages of 1% or below which may be interpreted as temporary NK cell deficiency. Findings on differences between active and inactive GPA were discrepant between vasculitis centers.ConclusionsNK cell counts and percentages in blood are highly variable. This variability is further enhanced in systemic inflammatory diseases, and includes patients with temporary NK cell deficiency, in particular in EGPA. NK cell counts and percentages can presently not be recommended as biomarker in clinical care of AAV patients.

scholarly journals Blood CD3-(CD56 or 16)+ natural killer cell distributions are heterogeneous in healthy adults and suppressed by azathioprine in patients with ANCA-associated vasculitides

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wolfgang Merkt ◽  
Ulrich Salzer ◽  
Jens Thiel ◽  
Ilona Jandova ◽  
Raoul Bergner ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Granulomatosis With Polyangiitis ◽  
Nk Cell ◽  
Clinical Care ◽  
Healthy Adults ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Azathioprine Therapy ◽  
Cell Counts ◽  
Healthy Donors

Abstract Background Cytotoxic Natural Killer (NK) cells are increasingly recognized as a powerful tool to induce targeted cell death in cancer and autoimmune diseases. Still, basic blood NK cell parameters are poorly defined. The aims of this study were 1) to establish reference values of NK cell counts and percentages in healthy adults; 2) to describe these parameters in the prototype autoimmune disease group ANCA-associated vasculitis (AAV); and 3) to investigate whether NK cell counts and percentages may be used as activity biomarkers in the care of AAV patients, as suggested by a preceding study. Methods CD3-(CD56 or 16)+ NK cell counts and percentages were determined in 120 healthy adults. Lymphocyte subset and clinical data from two German vasculitis centers were analyzed retrospectively (in total 407 measurements, including 201/49/157 measurements from 64/16/39 patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), respectively). Results CD3-(CD56 or 16)+ NK cell counts and percentages in healthy adults were highly variable, not Gaussian distributed and independent of age and sex. NK cell percentages ranged from 1.9 to 37.9% of lymphocytes, and were significantly more dispersed in AAV (0.3 to 57.6%), while the median percentage was not different between AAV and healthy donors. In contrast, median NK cell counts were significantly lower in AAV compared to healthy donors. Sub-group analyses revealed that NK cell counts were low independent of AAV entity and disease activity. Azathioprine therapy was associated with significantly lower NK cell counts and percentages compared to non-azathioprine therapies. In 13.6% of azathioprine-treated patients, percentages were </= 1% which may be interpreted as temporary NK cell deficiency. NK cell counts and percentages could not separate active from inactive AAV. Conclusions NK cell counts and percentages in blood are heterogeneous and can presently not be recommended as biomarker in clinical care of AAV patients. Azathioprine treatment was associated with significantly low NK cells. These findings may be relevant for the development of drugs that aim at exploiting NK cell cytotoxicity and may help to identify patients at risk to develop malignant or infectious co-morbidities.

scholarly journals Natural Killer Cells in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - A Review of the Literature

2022 ◽  
Vol 12 ◽  
Author(s):  
Sina Fuchs ◽  
Andrea Scheffschick ◽  
Iva Gunnarsson ◽  
Hanna Brauner
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Granulomatosis With Polyangiitis ◽  
Microscopic Polyangiitis ◽  
Lymphoid Cells ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Systemic Autoimmune Diseases ◽  
Anca Associated Vasculitis ◽  
And Function ◽  
Eosinophilic Granulomatosis

Anti-neutrophil cytoplasmic antibody (ANCA)- associated vasculitis (AAV) is a group of systemic autoimmune diseases characterized by inflammation of small- and medium-sized vessels. The three main types of AAV are granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). A growing number of studies focus on natural killer (NK) cells in AAV. NK cells are innate lymphoid cells with important roles in anti-viral and anti-tumor defense, but their roles in the pathogenesis of autoimmunity is less well established. In this review, we will present a summary of what is known about the number, phenotype and function of NK cells in patients with AAV. We review the literature on NK cells in the circulation of AAV patients, studies on tissue resident NK cells and how the treatment affects NK cells.

Long Lasting Alteration of Natural Killer Cells Post-Chemotherapy in Elderly Patients with Acute Myeloid Leukemia (AML).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1653-1653
Author(s):  
Daniel Olive ◽  
Nicolas Anfossi ◽  
Pascale Andre ◽  
Jerome Rey ◽  
Florence Orlanducci ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Elderly Patients ◽  
Nk Cells ◽  
Natural Killer ◽  
Cd8 T Cells ◽  
Nk Cell ◽  
Time Points ◽  
Early Stages ◽  
Cell Counts

Abstract Abstract 1653 Poster Board I-679 Background The immune system is involved in AML control and Natural Killer (NK) cells are among the most promising effectors. The therapeutic potential of NK cells has been revealed by the Killer Immunoglobulin Receptor (KIR) mismatch allogeneic transplant model where the anti-leukemic effect of the graft, is due to unleashed NK cells towards AML blasts, as suggested by enhanced in vitro lytic activity of KIR-HLA mismatched donor NK cells against recipient blasts (Miller et al. 2005; Ruggeri et al. 2002). Receptors involved in the function of NK cells against AML blasts have been identified (Pende et al., 2005). Some of these receptors are altered in AML patients at diagnosis and might be involved in the immune escape of AML blasts (Costello et al., 2002). However, the status of NK cells during early stages of patient's chemotherapy (CT) treatment is unknown. The present study monitored status of NK cells during early stages following patient's remission after CT that may be critical for their long lasting clinical response, and results might provide new targets for immunotherapy. Methods We enrolled 20 elderly patients (60 to 80 years old) with non promyelocytic AML in first CR following induction and pre-consolidation CT with normal renal and hepatic functions. Patient peripheral NK, gd T and CD8 T cells were analyzed before consolidation CT and every other week after treatment for 8 weeks. 6-colors flow cytometry was performed to investigate the expression of MHC receptors (CD158a, b, e, i, CD85j and NKG2A), activating receptors (NKp30, NKp46, NKG2D, CD16, DNAM-1, 2B4) as well as their differentiation status (perforin and granzyme expression). Their function, as determined by cytotoxicity (51Cr release and CD107 expression) and cytokine production (intracellular staining of IFN-g), was analyzed using purified NK cells stimulated by K562, or in redirected assays using NKp30, NKp46 and CD16 mAbs. Results NK cell counts were depressed away from the induction and pre-consolidation CT as compared to NK cell counts of age-matched controls (ctl) (95±107 NK/μL vs 229±91 NK/μL respectively); they were further depressed during the first 2 weeks post-consolidation CT (55±57 NK/μL), but were back to pre-consolidation CT level at 4 weeks (105±102 NK/μL). In contrast, CD8 T cells and gd T cells counts were normal even at early times post-CT. Expression of 2B4 was depressed at all time points. In contrast, NKp30 expression was lower at diagnosis and close to ctl level post-consolidation CT (p=0.0003) and NKp46 expression increased after CT (p<0.0001). Sizes of NK cell subsets expressing CD158a or CD158b in patients post-induction and consolidation CT were smaller than those of ctl (% CD158a+: p=0.003; % CD158b+: p=0.014). In contrast the NKG2A or CD85j positive NK cell subsets were either unchanged or slightly increased respectively at all time points (p=0.0015 for CD85j+). Moreover, sizes of perforin or granzyme positive NK cell subsets were increased in treated AML patients (% Granzyme+: p= 0.0125 and % Perforin+: p=0.0268). In addition, we observed an important heterogeneity in the expression of the surface receptors among patients that is currently analyzed with respect to the duration of the CR. Finally, NK cell cytoxicity was comparable at all time points to the one of age-matched ctl. In contrast, IFN-g secretion was decreased, at all time points, against K562 or in redirected assays using CD16 mAb and almost abolished using redirected assay with NKp30 mAb. Conclusions This study demonstrates that in elderly AML patients in CR after CT (1) several alterations are detected at all time points, (2) NK cell number is lower and (3) IFN-g secretion is impaired. However NK cytotoxic function is comparable to age-matched controls. The likely basis of the complex pattern of modifications might rely on an interplay between the direct and indirect effects of chemotherapy, activation of immune system, NK cell differentiation and its interaction with AML blasts. Altogether this study indicates that new immunotherapeutic approaches might be used to increase NK cell numbers and functions (cytotoxicity and IFN-g secretion) at early times post-CT in elderly patients with AML. Disclosures Romagne: Innate Pharma: Employment.

Natural Killer Cells Recovery After Consolidation Chemotherapy in Elderly Patients with Acute Myeloid Leukemia (AML)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2189-2189 ◽  
Author(s):  
Jerome Rey ◽  
Nicolas Anfossi ◽  
Pascale Andre ◽  
Jean-Marie Boher ◽  
Florence Orlanducci ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Nk Cells ◽  
Natural Killer ◽  
Immune Escape ◽  
Nk Cell ◽  
Residual Disease ◽  
Leukemic Cells ◽  
Consolidation Chemotherapy ◽  
Cell Counts

Abstract Abstract 2189 Background: Human Natural Killer (NK) cells are able to kill abnormal cells while preserving normal cells. Accumulating clinical and experimental data point toward a key role of these cells in the control and clearance of most if not all hematologic malignancies. Recent insights into NK have stimulated studies of innate immunity in haematological malignancies, as the role of NK cells in allogeneic transplantation. Better knowledge of the deficiencies of these effector cells can allow elaborating new protocols of immunotherapy in order to directly enhance their capacity to eliminate tumor cells. Hence, the mechanisms of recognition and killing of leukemic cells and their role in vivo have only been investigated very recently. Even though lysis of leukemic cells or leukemic cell lines by NK cells has been described in vitro, mechanisms underlying the interaction and destruction of these cells are not clearly defined. Some of these receptors are altered in AML patients at diagnosis and might be involved in the immune escape of AML blasts. However, the recovery of NK cells during consolidation chemotherapy treatment has not been studied. The present study monitored status of NK cells following patient's remission after chemotherapy in order to provide new targets for immunotherapy. Methods: We enrolled 29 elderly patients (mean: 70-years old) with non promyelocytic AML in first CR following induction and pre-consolidation chemotherapy. Patient peripheral NK cells were analyzed at diagnosis, before consolidation chemotherapy and every two weeks after treatment for 8 weeks. 6-colors flow cytometry was performed to investigate the expression of MHC receptors (CD158a, b, e, i, CD85j and NKG2A), activating receptors (NKp30, NKp46, NKG2D, CD16, DNAM-1, 2B4) as well as their differentiation status (perforin and granzyme expression). Their function, as determined by cytotoxicity (51Cr release and CD107 expression) and cytokine production (intracellular staining of IFN-g), was analyzed using purified NK cells stimulated by K562, or in redirected assays using NKp30, NKp46 and CD16 mAbs. The recovery of these receptors was then correlated with PFS and OS. Results: NK cell counts were depressed after induction and pre-consolidation chemotherapy as compared to NK cell counts of age-matched controls; they were further depressed during the first 2 weeks post-consolidation chemotherapy, but were back to pre-consolidation chemotherapy level at 4 weeks. NKp30 and NKp46 expression was lower at diagnosis as compared to controls but their levels restored progressively after induction and consolidation chemotherapy. NKG2D expression were depressed at pre-consolidation but increased after consolidation chemotherapy. For inhibitory receptors, CD158a or CD158b expressions were depressed at diagnosis, at post-induction and consolidation chemotherapy. In contrast, the NKG2A positive NK cell subsets increased progressively after consolidation chemotherapy. Moreover, sizes of perforin or granzyme positive NK cell subsets were increased in treated AML patients. K562 cytotoxicity was depressed after induction chemotherapy but increased after consolidation chemotherapy. In contrast, IFN-g secretion was decreased, at all time points. Finally, we try to correlate the recovery of these different receptors with OS and PFS. NKp30 and NKG2D recovery seems to be correlated with better PFS and OS. Conclusions: This study confirms that NK cells from AML patients displayed different phenotype and functional abnormalities at diagnosis. Chemotherapy seems to have different impact on the recovery of inhibitory or activatory NK receptors. The predominant data is that NK cells recovered rapidly after consolidation chemotherapy and seems to be more operational at that time. Immunotherapy of NK cells must be probably developed post consolidation chemotherapy when NK cells are ready and residual disease low. Antibodies to stimulate NK cells are actually evaluated in this setting. Disclosures: Anfossi: Innate Pharma: Employment. Andre:Innate Pharma: Employment. Breso:Innate Pharma: Employment. Perri:Innate Pharma: Employment. Romagne:Innate Pharma: Employment.

scholarly journals Natural Killer Cell Function Is Well Preserved in Asymptomatic Human Immunodeficiency Virus Type 2 (HIV-2) Infection but Similar to That of HIV-1 Infection When CD4 T-Cell Counts Fall

2006 ◽  
Vol 80 (5) ◽  
pp. 2529-2538 ◽  
Author(s):  
Samuel Victor Nuvor ◽  
Marianne van der Sande ◽  
Sarah Rowland-Jones ◽  
Hilton Whittle ◽  
Assan Jaye
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Human Immunodeficiency Virus Type ◽  
Nk Cell ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Ifn Γ ◽  
Hiv 1

ABSTRACT Natural killer (NK) cells are potent effectors of natural immunity and their activity prevents human immunodeficiency virus type 1 (HIV-1) viral entry and viral replication. We sought to determine whether NK immune responses are associated with different clinical course of HIV-1 and HIV-2 infections. A cross-sectional analysis of NK cell responses was undertaken in 30 HIV-1 and 30 HIV-2 subjects in each of three categories of CD4+-T-cell counts (>500, 200 to 500, and <200 cells/μl) and in 50 HIV-uninfected control subjects. Lytic activity and gamma interferon (IFN-γ) secretion were measured by chromium release and enzyme-linked immunospot assays, respectively. Flow cytometry was used to assess intracellular cytokines and chemokines. Levels of NK cytotoxicity were significantly higher in HIV-2 than in HIV-1 infections in subjects with high CD4+-T-cell counts and were similar to that of the healthy controls. In these HIV-2 subjects, cytolytic activity was positively correlated to NK cell count and inversely related to plasma viremia. Levels of intracellular MIP-1β, RANTES, tumor necrosis factor alpha, and IFN-γ produced by NK CD56bright cells were significantly higher in HIV-2- than HIV-1-infected subjects with high CD4+-T-cell counts but fell to similar levels as CD4 counts dropped. The data suggest efficient cytolytic and chemokine-suppressive activity of NK cells early in HIV-2 infection, which is associated with high CD4+ T-cell counts. Enhancement of these functions may be important in immune-based therapy to control HIV disease.

Indomethacin inhibits circulating PGE2 and reverses postexercise suppression of natural killer cell activity

1999 ◽  
Vol 276 (5) ◽  
pp. R1496-R1505
Author(s):  
Shawn G. Rhind ◽  
Greg A. Gannon ◽  
Masatoshi Suzui ◽  
Roy J. Shephard ◽  
Pang N. Shek
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Strenuous Exercise ◽  
Double Blind ◽  
Cell Counts ◽  
Ergometer Exercise

Natural killer (NK) cells are important in combating viral infections and cancer. NK cytolytic activity (NKCA) is often depressed during recovery from strenuous exercise. Lymphocyte subset redistribution and/or inhibition of NK cells via soluble mediators, such as prostaglandin (PG) E2 and cortisol, are suggested as mechanisms. Ten untrained (peak O2 consumption = 44.0 ± 3.5 ml ⋅ kg−1 ⋅ min−1) men completed at 2-wk intervals a resting control session and three randomized double-blind exercise trials after the oral administration of a placebo, the PG inhibitor indomethacin (75 mg/day for 5 days), or naltrexone (reported elsewhere). Circulating CD3−CD16+/56+NK cell counts, PGE2, cortisol, and NKCA were measured before, at 0.5-h intervals during, and at 2 and 24 h after a 2-h bout of cycle ergometer exercise (65% peak O2 consumption). During placebo and indomethacin conditions, exercise induced significant ( P < 0.0001) elevations of NKCA (>100%) and circulating NK cell counts (>350%) compared with corresponding control values. With placebo treatment, total NKCA was suppressed (28%; P < 0.05) 2 h after exercise, and a postexercise elevation (36%; P = 0.02) of circulating PGE2 was negatively correlated ( r = 0.475, P = 0.03) with K-562 tumor cell lysis. NK counts were unchanged in the postexercise period, but at this stage CD14+ monocyte numbers were elevated ( P < 0.0001). Indomethacin treatment eliminated the postexercise increase in PGE2 concentration and completely reversed the suppression of total and per CD16+56+NKCA 2 h after exercise. These data support the hypothesis that the postexercise reduction in NKCA reflects changes in circulating PGE2 rather than a differential lymphocyte redistribution.

scholarly journals Reduced levels of circulating natural killer cells in children with celiac disease

2020 ◽  
Vol 60 (3) ◽  
pp. 125-30
Author(s):  
Mehmet Agin ◽  
Eylem Sevinc ◽  
Erkan Dogan ◽  
Nergiz Sevinc
Keyword(s):  
Celiac Disease ◽  
Nk Cells ◽  
Cell Count ◽  
Natural Killer ◽  
Peripheral Blood ◽  
Nk Cell ◽  
Absolute Number ◽  
Gluten Free ◽  
Cell Counts ◽  
The Absolute

Background Celiac disease (CD) is an autoimmune disease characterized by malabsorption. Serologic testing for CD consists of Ig A type of antitissue transglutaminase (tTG), antiendomysium (EMA). These tests are helpful in monitoring adherence to the gluten-free diet (GFD). Natural killer (NK) cell count alterations have been reported in various diseases, such as cancer, Crohn’s disease, malnutrition, and autoimmune disorders. Objective To compare peripheral blood NK cell counts in children with celiac disease (CD) to healthy controls. The second aim was to analyze for possible correlations between NK cells (CD3-/CD16+, CD56+) and tissue transglutaminase (tTG)-IgA and tTG-IgG, as well as endomysial antibody EMA-IgA indicating gluten sensitivity. Methods Fifty children with CD were compared to 48 healthy children as controls, with similar age and sex distribution. Peripheral blood NK cell counts were measured by flow cytometry. Results The median (P25-P75) ages of the 50 celiac patients (23 male; 46%) and 48 controls (21 male; 44%) were 10 (2-17) years and 9 (3-17) years, respectively. Mean follow-up duration was 3 years, ranging from 1-10 years. All CD patients had positive tTG-IgA and EMA-IgA tests while it was negative in all (100 %) control patients. The absolute number of circulating CD16+ NK cells (259.52 vs. 1404.36 μ/L) and CD56+ NK cells (366.24 vs. 2440.46 μ/L) were significantly lower in the celiac group than the control group (P<0.05 for both). The absolute numbers of circulating white blood cells (7785 vs. 8165 μ/L) and lymphocytes (3106 vs. 3173 μ/L) were not significantly different between the celiac and control groups (P>0.05 for both). Correlation analysis between the absolute number of circulating NK cells and tTG-IgA, tTG-IgG, and EMA-IgA levels in CD patients revealed no significant relationships (P>0.05 for all). Conclusions Peripheral blood NK cell count were significantly lower in celiac patients than controls, hence, decreased NK cell counts may be an abnormal feature seen in autoimmune diseases. NK cell count in celiac patients had no significant correlations to tTG-IgA, tTG-IgG, or EMA-IgA levels. Therefore,  NK cell count  may be inappropriate marker for monitoring compliance to a gluten free diet.

scholarly journals Reduced levels of circulating natural killer cells in children with celiac disease

2020 ◽  
Vol 60 (3) ◽  
pp. 124-9
Author(s):  
Mehmet Agin ◽  
Eylem Sevinc ◽  
Erkan Dogan ◽  
Nergiz Sevinc
Keyword(s):  
Celiac Disease ◽  
Nk Cells ◽  
Cell Count ◽  
Natural Killer ◽  
Peripheral Blood ◽  
Nk Cell ◽  
Absolute Number ◽  
Gluten Free ◽  
Cell Counts ◽  
The Absolute

Background Celiac disease (CD) is an autoimmune disease characterized by malabsorption. Serologic testing for CD consists of Ig A type of antitissue transglutaminase (tTG), antiendomysium (EMA). These tests are helpful in monitoring adherence to the gluten-free diet (GFD). Natural killer (NK) cell count alterations have been reported in various diseases, such as cancer, Crohn’s disease, malnutrition, and autoimmune disorders. Objective To compare peripheral blood NK cell counts in children with celiac disease (CD) to healthy controls. The second aim was to analyze for possible correlations between NK cells (CD3-/CD16+, CD56+) and tissue transglutaminase (tTG)-IgA and tTG-IgG, as well as endomysial antibody EMA-IgA indicating gluten sensitivity. Methods Fifty children with CD were compared to 48 healthy children as controls, with similar age and sex distribution. Peripheral blood NK cell counts were measured by flow cytometry. Results The median (P25-P75) ages of the 50 celiac patients (23 male; 46%) and 48 controls (21 male; 44%) were 10 (2-17) years and 9 (3-17) years, respectively. Mean follow-up duration was 3 years, ranging from 1-10 years. All CD patients had positive tTG-IgA and EMA-IgA tests while it was negative in all (100 %) control patients. The absolute number of circulating CD16+ NK cells (259.52 vs. 1404.36 μ/L) and CD56+ NK cells (366.24 vs. 2440.46 μ/L) were significantly lower in the celiac group than the control group (P<0.05 for both). The absolute numbers of circulating white blood cells (7785 vs. 8165 μ/L) and lymphocytes (3106 vs. 3173 μ/L) were not significantly different between the celiac and control groups (P>0.05 for both). Correlation analysis between the absolute number of circulating NK cells and tTG-IgA, tTG-IgG, and EMA-IgA levels in CD patients revealed no significant relationships (P>0.05 for all). Conclusions Peripheral blood NK cell count were significantly lower in celiac patients than controls, hence, decreased NK cell counts may be an abnormal feature seen in autoimmune diseases. NK cell count in celiac patients had no significant correlations to tTG-IgA, tTG-IgG, or EMA-IgA levels. Therefore,  NK cell count  may be inappropriate marker for monitoring compliance to a gluten free diet.

Characteristics of Circulating Natural Killer Cells and Their Interferon-γ Production in Active Adult-onset Still Disease

2019 ◽  
Vol 46 (10) ◽  
pp. 1268-1276 ◽  
Author(s):  
Yasuhiro Shimojima ◽  
Dai Kishida ◽  
Ken-ichi Ueno ◽  
Satoru Ushiyama ◽  
Takanori Ichikawa ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Mononuclear Cells ◽  
Nk Cell ◽  
Adult Onset ◽  
Peripheral Blood Mononuclear ◽  
Cell Counts ◽  
Significant Difference ◽  
Ifn Γ ◽  
Still Disease

Objective.To investigate the characteristics of circulating natural killer (NK) cells and their interferon (IFN)-γ–producing ability in adult-onset Still disease (AOSD).Methods.Peripheral blood mononuclear cells were obtained from 22 patients in the acute phase of AOSD (acute AOSD); 7 of the 22 patients after treatment (remission AOSD), and 11 healthy controls (HC). NK cells and their IFN-γ expression levels were analyzed by flow cytometry. Additionally, the cytokine receptors of interleukin (IL)-12, IL-15, and IL-18 on NK cells were also evaluated.Results.The frequency of NK cells was significantly lower in acute AOSD than in HC. NK cell counts significantly increased in remission AOSD. Expression of IL-12 and IL-15 receptors on NK cells was significantly increased in acute AOSD, whereas that of IL-18 receptor indicated no significant difference among 3 groups. IFN-γ expression in NK cells was significantly higher in acute AOSD than in HC, and significantly decreased in remission AOSD. The absolute number of NK cells and IFN-γ–expressing NK cells revealed an inverse correlation with serum ferritin levels in acute AOSD. In 2 distinct subsets of NK cells, CD56dim NK cells significantly exhibited higher IFN-γ expression than CD56bright NK cells in acute AOSD.Conclusion.In acute AOSD, NK cells displayed lower proportion, whereas they had higher ability for IFN-γ production than in HC; moreover, upregulation of IL-12 and IL-15 receptors on NK cells may promote IFN-γ production. In addition, disease activity may be implicated in regulating the number of NK cells and IFN-γ–expressing NK cells in AOSD.

Intermediate-affinity interleukin-2 receptor expression predicts CD56bright natural killer cell expansion after daclizumab treatment in the CHOICE study of patients with multiple sclerosis

2011 ◽  
Vol 17 (12) ◽  
pp. 1441-1448 ◽  
Author(s):  
James P Sheridan ◽  
Ying Zhang ◽  
Katherine Riester ◽  
Meina T Tang ◽  
Lyubov Efros ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Nk Cells ◽  
Natural Killer ◽  
Treatment Period ◽  
Cell Expansion ◽  
Nk Cell ◽  
Interleukin 2 ◽  
Receptor Expression ◽  
Multiple Time ◽  
Cell Counts

Objective: The objective of this study was to evaluate whether interleukin-2 (IL-2) receptor expression on CD56bright natural killer (NK) cells predicted CD56bright NK cell expansion and therapeutic response to daclizumab (DAC) in multiple sclerosis (MS). Methods: DAC exposure, CD56bright NK cell counts, IL-2 receptor alpha (CD25) and beta (CD122) subunits, and new or enlarged lesions on brain MRI were measured in 64 subjects in a pharmacokinetic/pharmacodynamic substudy of the phase 2 CHOICE trial at multiple time points. Peripheral blood mononuclear cell (PBMC) samples were obtained from healthy subjects to assess the relationship among DAC treatment, intermediate affinity IL-2 signaling, and CD56bright NK cell expansion. Results: Increased CD56bright NK cell counts in DAC/interferon beta (IFNβ)-treated subjects were observed by day 14, the first post-dosing time point (mean [SD] ln{CD56bright NK cell count}: DAC high/IFNβ, 2.01 [1.25]; DAC low/IFNβ, 2.29 [1.06]; placebo/IFNβ, 1.01 [1.03]; adjusted p = 0.003), and persisted throughout the treatment period. Higher DAC dose predicted a faster rate of CD56bright NK cell expansion ( p < 0.001), but individual subjects’ increases in CD56bright NK cells from baseline levels were only weakly correlated with DAC exposure ( r2 = 0.167). Higher expression of the intermediate-affinity IL-2 receptor subunit (CD122) on CD56bright NK cells at baseline predicted fewer new gadolinium-enhanced (Gd+) lesions during the treatment period (1.77 vs. 0.62 adjusted mean new Gd+ lesions during weeks 8–24, lowest vs. highest quartile of percentage CD122+ CD56bright NK cells; p = 0.033) and a greater increase in CD56bright NK cell counts at the end of DAC dosing ( p = 0.029). Conclusion: CD56bright NK cell expansion after DAC treatment appears to reflect individual differences in the capacity for intermediate-affinity IL-2 signaling and could provide a basis for predicting clinical response to DAC in MS.

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