Altered Expression of TNF-α Signaling Pathway Proteins in Systemic Lupus Erythematosus

2010 ◽  
Vol 37 (8) ◽  
pp. 1658-1666 ◽  
Author(s):  
LANG-JING ZHU ◽  
CAROLINA LANDOLT-MARTICORENA ◽  
TIMOTHY LI ◽  
XIAO YANG ◽  
XUE-QING YU ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell ◽  
Lupus Erythematosus ◽  
Peripheral Blood ◽  
Signaling Molecules ◽  
T Cell Subsets ◽  
Rna Expression ◽  
Systemic Lupus ◽  
Altered Expression ◽  
Tnf Α

Objective.To investigate the expression of tumor necrosis factor receptors (TNFR1 and TNFR2) and adapter proteins (TRADD, RIP, and TRAF2) in peripheral blood mononuclear cell (PBMC) subsets from patients with systemic lupus erythematosus (SLE).Methods.PBMC were isolated from 45 SLE patients and 25 controls, and stained with labeled antibodies that enabled identification of various T cell, B cell, and monocyte subpopulations. Expression of TNF-related signaling molecules was measured by staining with labeled antibodies either directly or following fixation and permeabilization. Apoptosis was quantified using an anti-active caspase 3 antibody. RNA expression of TNF-related signaling molecules was assessed by quantitative RT-PCR and serum levels of TNF-α by ELISA.Results.SLE patients had increased levels of TNFR1, TNFR2, and TRAF2, together with decreased levels of RIP, on various B, CD4+ T, and CD8+ T cell subsets as compared to controls. This altered expression was seen in both naive and memory subpopulations, and reflected altered staining of the whole population rather than a subset of cells that were activated. The levels of these molecules were not significantly correlated with serum TNF-α levels or their RNA expression in whole peripheral blood. TNFR1 and TNFR2 expression was negatively correlated with disease activity. There was no association between the proportion of apoptotic cells in any of the subpopulations and serum TNF-α levels or expression of TNF-related signaling molecules.Conclusion.Patients with SLE had altered expression of TNF-related signaling molecules, suggesting that there may be an imbalance in TNF-α signaling favoring cellular activation as opposed to proapoptotic pathways.

scholarly journals AB0343 THE CHARACTERISTICS OF T CELLS IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS WITH ANXIETY BASED ON MACHINE LEARNING

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1196.2-1197
Author(s):  
X. Gu ◽  
Y. Jin ◽  
R. Li ◽  
D. Zhang ◽  
C. Dong ◽  
...  
Keyword(s):  
Machine Learning ◽  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
Lupus Erythematosus ◽  
Peripheral Blood ◽  
Treg Cells ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Systemic Lupus

Background:Systemic lupus erythematosus (SLE) is an autoimmune disease, the immune system of patients to be disordered, especially in T cell subsets1. They were prone to mental diseases, anxiety particularly, which lead to suicide2. The recent study had reported that CD4+ T cells in the peripheral blood played the key role in like anxiety behavior of mice3. Although there showed that the level of serum TNF-α in SLE patients with anxiety was higher than without anxiety4, finding the important special mediators especially in T cell subsets was still necessary for the prevention of anxiety in SLE patients.Objectives:In total, 108 SLE patients, which met the diagnostic criteria of the American Society of rheumatology (v1997), were enrolled in this study from Affilliated Hospital of Nantong University, China. Exclusion criteria included other autoimmune diseases and active infection (including hepatitis B or C virus, Epstein-Barr virus, human immunodeficiency virus or Mycobacterium tuberculosis infection).Methods:We surveyed the abundance of 74 immune cell subpopulations from 108 SLE patients using flow cytometry, and investigated their differences between patients with and without anxiety (24 versus 84). Moreover, machine learning including Lasso regression, Random forest (RF) and Sparsity partial least squares discriminant analysis (sPLS-DA) was employed to build models and futher selected important features for the classification of SLE patients with anxiety.Results:SLE patients with anxiety showed higher body mass index (BMI) and lower quality of life. In their peripheral blood, the proportion of internal cell subsets composition of Th cell and Treg cells changed. By machine learning, we finally found that BMI and PD1-CD28- Treg played important rules to developing lupus anxiety.Conclusion:In this study, machine learning was applied to build models to select the most important T cell subset in SLE patients with anxiety. These findings suggested that BMI and imbalance of PD1-CD28- Treg containing effector memory Treg cells and effector Treg cells mostly played important roles in the development of SLE anxiety.Disclosure of Interests:None declared

scholarly journals CD3+CD4+gp130+ T Cells Are Associated With Worse Disease Activity in Systemic Lupus Erythematosus Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Nur Diyana Mohd Shukri ◽  
Aziz Farah Izati ◽  
Wan Syamimee Wan Ghazali ◽  
Che Maraina Che Hussin ◽  
Kah Keng Wong
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Lymphocyte Subpopulations ◽  
Gene Set Enrichment Analysis ◽  
T Cell Subsets ◽  
Healthy Controls ◽  
Systemic Lupus

The receptors for IL-35, IL-12Rβ2 and gp130, have been implicated in the inflammatory pathophysiology of autoimmune diseases. In this study, we set out to investigate the serum IL-35 levels and the surface levels of IL-12Rβ2 and gp130 in CD3+CD4+, CD3+CD4─ and CD3─CD4─ lymphocyte subpopulations in systemic lupus erythematosus (SLE) patients (n=50) versus healthy controls (n=50). The potential T cell subsets associated with gp130 transcript (i.e. IL6ST) expression in CD4+ T cells of SLE patients was also examined in publicly-available gene expression profiling (GEP) datasets. Here, we report that serum IL-35 levels were significantly higher in SLE patients than healthy controls (p=0.038) but it was not associated with SLEDAI-2K scores. The proportions of IL-12Rβ2+ and gp130+ cells in SLE patients did not differ significantly with those of healthy controls in all lymphocyte subpopulations investigated. Essentially, higher SLEDAI-2K scores were positively correlated with increased proportion of gp130+ cells, but not IL-12Rβ2+ cells, on CD3+CD4+ T cells (r=0.425, p=0.002, q=0.016). Gene Set Enrichment Analysis (GSEA) of a GEP dataset of CD4+ T cells isolated from SLE patients (n=8; GSE4588) showed that IL6ST expression was positively associated with genes upregulated in CD4+ T cells vs myeloid or B cells (q<0.001). In an independent GEP dataset of CD4+ T cells isolated from SLE patients (n=9; GSE1057), IL6ST expression was induced upon anti-CD3 stimulation, and that Treg, TCM and CCR7+ T cells gene sets were significantly enriched (q<0.05) by genes highly correlated with IL6ST expression (n=92 genes; r>0.75 with IL6ST expression) upon anti-CD3 stimulation in these SLE patients. In conclusion, gp130 signaling in CD3+CD4+ T cell subsets may contribute to increased disease activity in SLE patients, and it represents a promising therapeutic target for inhibition in the disease.

scholarly journals Detection of Antilymphocyte Antibody with Two-Color Method in Systemic Lupus Erythematosus and Its Heterogeneous Specificities against Human T-Cell Subsets

1979 ◽  
Vol 64 (5) ◽  
pp. 1213-1220 ◽  
Author(s):  
Kunio Okudaira ◽  
Hidenori Nakai ◽  
Tetsuo Hayakawa ◽  
Takamichi Kashiwado ◽  
Kiyoaki Tanimoto ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell ◽  
Lupus Erythematosus ◽  
T Cell Subsets ◽  
Systemic Lupus ◽  
Human T Cell ◽  
Antilymphocyte Antibody

scholarly journals A defect of immunoregulatory T cell subsets in systemic lupus erythematosus patients demonstrated with anti-2H4 antibody.

1987 ◽  
Vol 79 (3) ◽  
pp. 762-768 ◽  
Author(s):  
C Morimoto ◽  
A D Steinberg ◽  
N L Letvin ◽  
M Hagan ◽  
T Takeuchi ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell ◽  
Lupus Erythematosus ◽  
T Cell Subsets ◽  
Systemic Lupus

Imbalance between CD8+CD28+ and CD8+CD28– T-cell subsets and its clinical significance in patients with systemic lupus erythematosus

Lupus ◽  
2019 ◽  
Vol 28 (10) ◽  
pp. 1214-1223
Author(s):  
S Minning ◽  
Y Xiaofan ◽  
X Anqi ◽  
G Bingjie ◽  
S Dinglei ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
Lupus Erythematosus ◽  
Fas Ligand ◽  
Activity Index ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Systemic Lupus ◽  
T Cell Subset

Objective The aim of this study was to evaluate the changes in CD8+CD28–/CD8+CD28+ T-cell subset balance and in the CD8+CD28– Treg cell number and function in patients with systemic lupus erythematosus (SLE). Methods Cell isolation and flow cytometry analysis were employed to investigate the T-cell subsets. Results It was found that in high-activity SLE patients, the CD8+CD28+ T-cell subset was reduced, which was inversely correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and that the CD8+CD28–/CD8+CD28+ ratio was elevated, which was positively correlated with SLEDAI and with renal damage and inversely correlated with serum complement level, whereas the CD8+CD28– T-cell subset was increased only in inactive patients. It was also found that apoptosis of CD8+ T cells increased, and Fas, Fas ligand (FasL) and interleukin (IL)-6 expression were high, whereas cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) expression was low by the CD8+CD28+ T cell subset in active SLE patients; apoptosis was positively correlated with SLEDAI and with the expression of Fas and FasL by the CD8+CD28+ T-cell subset in active SLE patients. IL-6 and CTLA-4 expression were found to be low by the CD8+CD28– T cell subset in active SLE patients. Conclusion These data suggest that high expression of Fas, FasL and IL-6 and low expression of CTLA-4 by the CD8+CD28+ T-cell subset promotes the activation-induced cell death of the CD8+CD28+ T-cell subset, resulting in an imbalance of CD8+CD28–/CD8+CD28+ T cells in active SLE patients, which represents an important feature in the immunological pathogenesis of SLE. The CD8+CD28– T-cell subset may play some role in inactive SLE.

Regulatory T-cell levels in systemic lupus erythematosus patients: a meta-analysis

Lupus ◽  
2019 ◽  
Vol 28 (4) ◽  
pp. 445-454 ◽  
Author(s):  
Y Zhu ◽  
Y Huang ◽  
B Ming ◽  
X Wu ◽  
Y Chen ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Ethnic Groups ◽  
Lupus Erythematosus ◽  
Subgroup Analysis ◽  
Peripheral Blood ◽  
Meta Analysis ◽  
Systemic Lupus

Background The contribution of regulatory T-cells (Tregs) to systemic lupus erythematosus (SLE) pathogenesis remains a matter of debate. The objective of this study was to quantify the association between peripheral blood Tregs and disease status in SLE patients. Method EMBASE and PubMed databases were searched using ‘systemic lupus erythematosus’ and ‘regulatory T-cells’ as relevant key terms. A meta-analysis of studies that examined the proportion of Tregs among peripheral blood mononuclear cells (PBMCs) and CD4+T-cells was performed using Stata software. Subgroup analysis was performed based on ethnic groups and Treg definition markers. Results The Treg/PBMC and Treg/CD4+T-cell ratios were significantly lower in SLE patients than in healthy controls (HCs), whereas patients with active and inactive SLE showed no difference in these indicators. A subgroup analysis indicated that Asian SLE patients had a substantially lower proportion of Tregs/PBMCs than HCs, but this difference was not seen for white and Latin American SLE patients. Patients defined by CD4+CD25+Foxp3+, CD4+CD25+ and CD4+Foxp3+ had a much lower Treg/PBMC ratio compared with HCs. Ethnic groups and choice of Treg definition markers had no influence on the proportion of Tregs/CD4+T-cells. Conclusion The proportion of Tregs among both PBMCs and CD4+T-cells was significantly decreased in SLE patients. Ethnic group and Treg definition markers may influence the proportion of Tregs among PBMCs. Further study of the correlation between SLE disease activity and the proportion of Tregs in peripheral blood is needed to determine the physiological role of this association.

Low-dose interleukin-2 treatment selectively modulates CD4+ T cell subsets in patients with systemic lupus erythematosus

2016 ◽  
Vol 22 (9) ◽  
pp. 991-993 ◽  
Author(s):  
Jing He ◽  
Xia Zhang ◽  
Yunbo Wei ◽  
Xiaolin Sun ◽  
Yaping Chen ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell ◽  
Lupus Erythematosus ◽  
Low Dose ◽  
Interleukin 2 ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Systemic Lupus
Sign in / Sign up

Export Citation Format

Share Document