scholarly journals Cytometric Characterization of Main Immunocompetent Cells in Patients with Systemic Sclerosis: Relationship with Disease Activity and Type of Immunosuppressive Treatment

2019 ◽  
Vol 8 (5) ◽  
pp. 625 ◽  
Author(s):  
Olga Gumkowska-Sroka ◽  
Krystyna Jagoda ◽  
Aleksander Owczarek ◽  
Grzegorz Helbig ◽  
Joanna Giemza-Stokłosa ◽  
...  

Systemic sclerosis (SSc) is a connective tissue disease that is characterized by widespread skin and internal organ fibrosis vasculopathy and immune response abnormalities, including T, B, natural killer (NK), and natural killer T (NKT) cell involvement. The aim of the study was to investigate the immune cell profile in patients with systemic sclerosis in relation to the disease activity, severity, and antibody presence and their relation to the type of immunosuppressive treatment. Cytometric examination identified following cell lines: B cells (Breg, B memory, B mature) and plasmablasts, T cell, T double positive—Tdp, T double negative—Tdn, NK, and NKT cell and monocytes. The disease severity and activity were assessed based on the Medsger and the EULAR Scleroderma Trials and Research Group (EUSTAR) 2017 scales respectively. In the study, SSc patients were characterized by higher total lymphocyte count parallel to increased frequency of Ts and Th cells. In SSc patients, increment of Tdp and reduction of Tdn as well as NK and NKT cells were observed. Additionally in SSc patients the reduction of B memory was noted. Head to head comparison between cyclophosphamide (CYC) and mycophenolate mofetil (MMF) treatment showed a reduction of CD19+ cells, but increment of plasmablasts in CYC treated patients.

2019 ◽  
Vol 68 (6) ◽  
pp. 1011-1024 ◽  
Author(s):  
Daniëlle Krijgsman ◽  
Natasja L. de Vries ◽  
Anni Skovbo ◽  
Morten N. Andersen ◽  
Marloes Swets ◽  
...  

2003 ◽  
Vol 77 (3) ◽  
pp. 2251-2257 ◽  
Author(s):  
Michaela Lucas ◽  
Stephan Gadola ◽  
Ute Meier ◽  
Neil T. Young ◽  
Gillian Harcourt ◽  
...  

ABSTRACT Natural killer T (NKT) cells are thought to be involved in innate responses against infection. We investigated one specific type of NKT cell, Vα24/Vβ11 double positive, in hepatitis C virus (HCV) infection. Lower frequencies of this population were detected in the blood of HCV PCR-positive patients than in controls. Unlike Vα24/Vβ11 NKT cells found in blood, those in the liver appeared to be recently activated.


Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 650 ◽  
Author(s):  
Maia Chiokadze ◽  
Christin Bär ◽  
Jana Pastuschek ◽  
Boris V. Dons’koi ◽  
Kseniia G. Khazhylenko ◽  
...  

Changes in the number and cytotoxic potential of uterine Natural Killer (uNK) cells have been associated with reduced fertility. To provide a better characterization of immunophenotypes in the endometrium of women with uRPL (unexplained recurrent pregnancy loss), we examined the applicability of a set of five immune cell markers. The concentration (cells/mm2) of CD45+ leukocytes, CD56+ uNK cells, and CD138+ plasma cells as well as of CD16+ and CD57+ cells, which indicate high cytotoxic uNK cells, were assessed by immunohistochemistry in endometrial biopsies from 61 uRPL patients and 10 controls. Control fertile endometria presented 90–300 CD56+ uNK cells/mm2. uRPL cases were classified in subgroups of low (uRPL-CD56low < 90 cells/mm2), normal (uRPL-CD56normal 90–300 cells/mm2), and high uNK cell counts (uRPL-CD56high > 300 cells/mm2). Some cases from the uRPL-CD56low and uRPL-CD56normal subgroups showed elevated proportions of cytotoxic CD16+ and CD57+ cells in relation to CD56+ cells. In the uRPL-CD56high subgroup, the CD57/CD56 ratio was reduced in most samples and the CD16/CD56 ratio was unaltered. Analysis of CD138 excluded the influence of chronic endometritis on these observations. Our results reinforce a link between uRPL and a dysfunctional endometrial environment associated with distinct immune cell profiles.


Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 514
Author(s):  
Denise Utami Putri ◽  
Cheng-Hui Wang ◽  
Po-Chun Tseng ◽  
Wen-Sen Lee ◽  
Fu-Lun Chen ◽  
...  

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.


Author(s):  
Leoni Rolfes ◽  
Tobias Ruck ◽  
Christina David ◽  
Stine Mencl ◽  
Stefanie Bock ◽  
...  

AbstractRag1−/− mice, lacking functional B and T cells, have been extensively used as an adoptive transfer model to evaluate neuroinflammation in stroke research. However, it remains unknown whether natural killer (NK) cell development and functions are altered in Rag1−/− mice as well. This connection has been rarely discussed in previous studies but might have important implications for data interpretation. In contrast, the NOD-Rag1nullIL2rgnull (NRG) mouse model is devoid of NK cells and might therefore eliminate this potential shortcoming. Here, we compare immune-cell frequencies as well as phenotype and effector functions of NK cells in Rag1−/− and wildtype (WT) mice using flow cytometry and functional in vitro assays. Further, we investigate the effect of Rag1−/− NK cells in the transient middle cerebral artery occlusion (tMCAO) model using antibody-mediated depletion of NK cells and adoptive transfer to NRG mice in vivo. NK cells in Rag1−/− were comparable in number and function to those in WT mice. Rag1−/− mice treated with an anti-NK1.1 antibody developed significantly smaller infarctions and improved behavioral scores. Correspondingly, NRG mice supplemented with NK cells were more susceptible to tMCAO, developing infarctions and neurological deficits similar to Rag1−/− controls. Our results indicate that NK cells from Rag1−/− mice are fully functional and should therefore be considered in the interpretation of immune-cell transfer models in experimental stroke. Fortunately, we identified the NRG mice, as a potentially better-suited transfer model to characterize individual cell subset-mediated neuroinflammation in stroke.


Lupus ◽  
2021 ◽  
pp. 096120332199010
Author(s):  
Vineeta Shobha ◽  
Anu Mohan ◽  
AV Malini ◽  
Puneet Chopra ◽  
Preethi Karunanithi ◽  
...  

Objective Despite the significant advancement in the understanding of the pathophysiology of systemic lupus erythematosus (SLE) variable clinical response to newer therapies remain a major concern, especially for patients with lupus nephritis and neuropsychiatric systemic lupus erythematosus (NPSLE). We performed this study with an objective to comprehensively characterize Indian SLE patients with renal and neuropsychiatric manifestation with respect to their gene signature, cytokine profile and immune cell phenotypes. Methods We characterized 68 Indian SLE subjects with diverse clinical profiles and disease activity and tried to identify differentially expressed genes and enriched pathways. To understand the temporal profile, same patients were followed at 6 and 12-months intervals. Additionally, auto-antibody profile, levels of various chemokines, cytokines and the proportion of different immune cells and their activation status were captured in these subjects. Results Multiple IFN-related pathways were enriched with significant increase in IFN-I gene signature in SLE patients as compared to normal healthy volunteers (NHV). We identified two transcriptionally distinct clusters within the same cohort of SLE patients with differential immune cell activation status, auto-antibody as well as plasma chemokines and cytokines profile. Conclusions Identification of two distinct clusters of patients based on IFN-I signature provided new insights into the heterogeneity of underlying disease pathogenesis of Indian SLE cohort. Importantly, patient within those clusters retain their distinct expression dynamics of IFN-I signature over the time course of one year despite change in disease activity. This study will guide clinicians and researchers while designing future clinical trials on Indian SLE cohort.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 482.2-483
Author(s):  
A. Alshevskaya ◽  
J. Lopatnikova ◽  
J. Zhukova ◽  
O. Chumasova ◽  
N. Shkaruba ◽  
...  

Background:The balance of TNFα receptors expression on cells which are actively involved in immunopathological processes affects both the density of distribution of receptors on cells and co-expression in subsets. Previously it was shown that basic effective RA therapy with methotrexate and glucocorticoids leads to equalization of the expression profile either in the percentage of cells or in the number of receptors, approaching those of healthy donors, but not simultaneously. However, questions about the relationship between the effectiveness of biological therapy and receptors co-expression remain unknown.Objectives:To assess the differences in co-expression and quantitative expression of TNF receptors type 1 and 2 in subsets of cells associated with the severity of the disease, depending on the response to rituximab therapy.Methods:Subanalysis of patients with high disease activity level successfully treated with rituximab (alone or in combination treatment scheme) during hospitalization was performed (n = 14). The first group included 6 patients who retained low disease activity during 1 month follow-up (RA, stabilization). The second group consisted of 8 patients who had exacerbation during follow-up period. As a control group, we used data from 43 comparable healthy donors. Subsets of T regulatory cells and monocytes were studied. A comparison was made among the indicators of receptors number and proportion of cells expressing the corresponding receptor.Results:For T regulatory cells, the key differences for patients who did not retain low disease activity were significantly higher number of TNF type 1 and type 2 receptors on double-positive cells with a lower percentage of these cells compared to stable patients. At the same time, higher differences between proportions of double-positive cells in comparison with control values of healthy donors were associated with higher probability of maintaining in remission.For monocytes, the key differences in stable patients were the very high quantitative expression of type 1 receptors on double-positive cells, with a lower percentage of these cells compared to patients with exacerbation. At the same time, lower differences between proportions of double-positive cells in comparison with control values of healthy donors were associated with higher probability of maintaining in remission.Conclusion:Obtained data confirm the previously proposed hypothesis about the essential role of balance in quantitative expression of TNF receptors type 1 and 2 on double-positive cells to determine the intensity and type of cell response to the mediator and its association with the level of disease activity and response to therapy.Acknowledgements:This study is supported by grant of the President of the Russian Federation for state support of young Russian PhD scientists №МК-2433.2020.4Disclosure of Interests:None declared


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