scholarly journals Aberrant expression of PD-1 on B cells and their subpopulations in systemic lupus erythematosus and association with clinical parameters

2019 ◽  
Author(s):  
xie changhao ◽  
Yang Lu ◽  
Qingqing Zhu ◽  
Yun Li ◽  
Qiyi Wang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Activity Index ◽  
Clinical Parameters ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Aberrant Expression

Abstract Background: The binding of programmed death 1 (PD-1) with its ligands inhibits the T cell activation and proliferation. But role of the PD-1 pathway on B cells is unclear. In present study, we aimed to evaluate the expression of PD-1 on B cells and their subpopulations and association with clinical parameters in systemic lupus erythematosus (SLE).Results: The frequency of B cells increased significantly in patients with active SLE compared with healthy controls and patients with inactive SLE.The proportions of CD19+ IgD- CD27- cells andplasmablast cell among total B cells were significantly higher in patients with SLE compared with controls. The percentage of PD-1+ B cells was higher in patients with in active SLE than in healthy controls. The proportion of PD-1+ B cells was correlated with lupus nephritis, complement components, IgG, SLE Disease Activity Index, and autoantibodies. PD-1+ B cells from SLE showed a high proliferative response. The levels of IgG and anti-dsDNA secreted by PD-1+ B cells from SLE patients was higher after 7 days compared with that by PD-1- B cells from patients with SLE and healthy controls.Conclusions: The expression of PD-1 on B cells and their subpopulations was aberrant and was associated with clinical parameters in SLE.KEY WORDS:PD-1; B cells; subpopulation; systemic lupus erythematosus

scholarly journals Aberrant expression of PD-1 on B cells and its association with the clinical parameters of systemic lupus erythematosus

2020 ◽  
Author(s):  
Yang Lu ◽  
Qingqing Zhu ◽  
Yun Li ◽  
Qiyi Wang ◽  
Chao Jiang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
B Cell ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Expression Patterns ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Aberrant Expression ◽  
Cell Subpopulations

Abstract Background: Programmed death 1 (PD-1) is an immunoregulatory receptor that inhibits T cell activation and proliferation upon binding to its cognate ligand (PD-L1). However, the role of the PD-1/PD-L1 axis in B cell function, especially in inflammatory and autoimmune disorders, is less clear. The aim of this study was to analyze the PD-1 expression patterns on multiple B cell subpopulations isolated from systemic lupus erythematosus (SLE) patients, and determine their clinical relevance. Results: The frequency of B cells increased significantly in patients with active SLE compared with healthy controls and patients with inactive SLE. In particular, the frequencies of the IgD CD27 and IgD CD27high (plasmablast cells) subpopulations were significantly higher in the patients compared to healthy individuals. Interestingly, the patients with active SLE harbored an increased proportion of the PD-1+ B cells, which correlated significantly with the disease severity (SLEDAI scores), incidence of lupus nephritis, and the circulating levels of autoantibodies and complement factors. Furthermore, the primary PD-1+ B cells isolated from the peripheral blood of SLE patients proliferated faster and secreted more anti-dsDNA antibodies and immunoglobulins in vitro compared to the PD-1+/- B cells from healthy controls. Conclusions: PD-1 is overexpressed on all B cell subpopulations of SLE patients and associated with disease progression.

RNA-seq of circular RNAs identified circPTPN22 as a potential new activity indicator in systemic lupus erythematosus

Lupus ◽  
2019 ◽  
Vol 28 (4) ◽  
pp. 520-528 ◽  
Author(s):  
Q Miao ◽  
Z Zhong ◽  
Z Jiang ◽  
Y Lin ◽  
B Ni ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Activity Index ◽  
Circular Rnas ◽  
Healthy Controls ◽  
Rna Seq ◽  
Systemic Lupus ◽  
Aberrant Expression

Background Circular RNAs (circRNAs) are possible biomarkers for many diseases, but the knowledge of circRNAs in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) remains limited. This study aimed to assess the expression of circRNAs in PBMCs from patients with SLE and healthy individuals by RNA sequencing (RNA-seq). Methods In total, 128 circRNAs were significantly differentially expressed including 39 upregulated and 89 downregulated circRNAs in four new-onset SLE patients compared with three healthy controls. After verification of the four candidate circRNAs in 49 patients with SLE and 37 controls using quantitative real-time polymerase chain reaction (qRT-PCR) assays, a previously undescribed circRNA with potential translation activity, circPTPN22, was selected to confirm its clinical significance. Results Bioinformatics analysis demonstrated that the parent gene of circPTPN22 was protein tyrosine phosphatase non-receptor type 22 (PTPN22), a potent regulator of T cell activation. The downregulation of circPTPN22 in patients with SLE was strongly negatively correlated with their Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores. circRNA-miRNA-mRNA co-expression network analysis indicated a correlation between circPTPN22 and the miRNAs and mRNAs related to immunological regulation including the development of SLE. Patients with higher SLEDAI scores had lower circPTPN22 expression levels, and long-term hormone treatment significantly increased circPTPN22 levels. Receiver operating characteristic curve analysis indicated that circPTPN22 has good diagnostic value for SLE. Conclusion Our data demonstrated the aberrant expression of circRNAs in patients with SLE compared with healthy controls; circPTPN22 might function as a diagnostic and disease severity indicator in SLE.

scholarly journals Cytokine Overproduction, T-Cell Activation, and Defective T-Regulatory Functions Promote Nephritis in Systemic Lupus Erythematosus

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Marco Tucci ◽  
Stefania Stucci ◽  
Sabino Strippoli ◽  
Francesco Silvestris
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
B Cells ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Cell Function ◽  
Inflammatory Cells ◽  
Systemic Lupus ◽  
Regulatory Functions

Lupus nephritis (LN) occurs in more than one-third of patients with systemic lupus erythematosus. Its pathogenesis is mostly attributable to the glomerular deposition of immune complexes and overproduction of T helper- (Th-) 1 cytokines. In this context, the high glomerular expression of IL-12 and IL-18 exerts a major pathogenetic role. These cytokines are locally produced by both macrophages and dendritic cells (DCs) which attract other inflammatory cells leading to maintenance of the kidney inflammation. However, other populations including T-cells and B-cells are integral for the development and worsening of renal damage. T-cells include many pathogenetic subsets, and the activation of Th-17 in keeping with defective T-regulatory (Treg) cell function regards as further event contributing to the glomerular damage. These populations also activate B-cells to produce nephritogenic auto-antibodies. Thus, LN includes a complex pathogenetic mechanism that involves different players and the evaluation of their activity may provide an effective tool for monitoring the onset of the disease.

Elevated levels of IL-24 in systemic lupus erythematosus patients

Lupus ◽  
2019 ◽  
Vol 28 (6) ◽  
pp. 748-754 ◽  
Author(s):  
R C Li ◽  
J Guo ◽  
L C Su ◽  
A F Huang
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Inflammatory Cytokine ◽  
Activity Index ◽  
Clinical Manifestations ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Good Ability

Objective This study aimed to assess IL-24 levels and their association with clinical manifestations in patients with systemic lupus erythematosus (SLE). Methods There were 75 patients with SLE and 58 healthy controls recruited in this study. Serum levels of IL-24 were measured by enzyme-linked immunosorbent assays, and mRNA levels of IL-24 were tested by quantitative real-time polymerase chain reaction . The area under the curve of the receiver operating characteristic (ROC) curve was used for diagnostic ability of the inflammatory cytokine. Results Serum IL-24 levels were significantly higher in SLE patients than that in healthy controls. SLE patients with nephritis had higher IL-24 levels than those without nephritis. Active SLE patients showed higher expression of IL-24 as compared to less active disease patients. The mRNA levels of IL-24 were much higher in SLE patients. Correlation analysis showed significant correlation between serum IL-24 levels and SLE disease activity index. In addition, ROC analysis may suggest good ability of serum IL-24 in differentiating SLE. Conclusion The inflammatory cytokine correlated with SLE disease activity, and may be involved in this disease pathogenesis.

scholarly journals Carbon monoxide inhibits T cell activation in target organs during systemic lupus erythematosus

2015 ◽  
Vol 182 (1) ◽  
pp. 1-13 ◽  
Author(s):  
J. P. Mackern-Oberti ◽  
J. Obreque ◽  
G. P. Méndez ◽  
C. Llanos ◽  
A. M. Kalergis
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Carbon Monoxide ◽  
T Cell ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Systemic Lupus ◽  
Target Organs

Abstract MP41: A Role Of Isolevuglandins In Systemic Lupus Erythematosus Associated Autoimmunity And Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
David M Patrick ◽  
Nestor de la Visitacion ◽  
Michelle J Ormseth ◽  
Charles Stein ◽  
Sean S Davies ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Immune Cell ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Immune Cell Activation ◽  
Systemic Immune Activation

Essential hypertension and systemic lupus erythematosus (SLE) are devastating conditions that disproportionately affect women. SLE has heterogeneous manifestations and treatment is limited to the use of non-specific global immunosuppression. Importantly, there is an increased prevalence of hypertension in women with SLE compared to healthy controls. Isolevuglandins (IsoLGs) are oxidation products of fatty acids that form as a result of reactive oxygen species. These molecules adduct covalently to lysine residues of proteins. Adducted proteins are then presented as autoantigens to T-cells resulting in immune cell activation. Previous studies have shown an essential role of IsoLGs in immune cell activation and the development of hypertension in animal models. We hypothesize that isoLGs are important for the development of hypertension and systemic immune activation in SLE. We first examined isoLG adduct accumulation within monocytes of human subjects with SLE compared to healthy controls. By flow cytometry, we found marked accumulation of isoLG adducts within CD14 + monocytes (34.2% ± 12.4% vs 3.81% ± 2.1% of CD14 + , N = 10-11, P <0.05). We confirmed this increase in isoLG adducts by mass spectrometry. To determine a causative role of isoLG adducts in immune activation and hypertension in SLE, we employed the B6.SLE123 and NZBWF1 mouse models of SLE. Animals were treated with the isoLG scavenger 2-hydroxybenzylamine (2-HOBA) or vehicle beginning at 7 weeks and were sacrificed at 32 weeks of age. C57BL/6 and NZW were used as controls. Importantly, treatment with 2-HOBA attenuated blood pressure in both mouse models (systolic BP 136.2 ± 5.6 mmHg for B6.SLE123 vs 120.9 ± 4.46 mmHg for B6.SLE123 +2HOBA; 164.7 ± 24.4 mmHg for NZBWF1 vs 136.9 ± 14.9 mmHg for NZBWF1 +2HOBA, N = 6-8, P < 0.05). Moreover, treatment with 2-HOBA reduced albuminuria and renal injury in the B6.SLE123 model (albumin/creatinine ratio 33.8 ± 2.0 x 10 -2 μg/mg for B6.SLE123 vs 5.5 ± 0.9 x 10 -2 μg/mg for B6.SLE123 +2HOBA, N = 7-9, P < 0.05). Finally, immune cell accumulation in primary and secondary lymphoid organs is significantly attenuated by 2-HOBA. These studies suggest a critical role of isoLG adduct accumulation in both systemic immune activation and hypertension in SLE.

scholarly journals MAP4K Family Kinases and DUSP Family Phosphatases in T-Cell Signaling and Systemic Lupus Erythematosus

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1433 ◽  
Author(s):  
Chuang ◽  
Tan
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
Cell Signaling ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Therapeutic Targets ◽  
T Cell Signaling ◽  
Systemic Lupus

T cells play a critical role in the pathogenesis of systemic lupus erythematosus (SLE), which is a severe autoimmune disease. In the past 60 years, only one new therapeutic agent with limited efficacy has been approved for SLE treatment; therefore, the development of early diagnostic biomarkers and therapeutic targets for SLE is desirable. Mitogen-activated protein kinase kinase kinase kinases (MAP4Ks) and dual-specificity phosphatases (DUSPs) are regulators of MAP kinases. Several MAP4Ks and DUSPs are involved in T-cell signaling and autoimmune responses. HPK1 (MAP4K1), DUSP22 (JKAP), and DUSP14 are negative regulators of T-cell activation. Consistently, HPK1 and DUSP22 are downregulated in the T cells of human SLE patients. In contrast, MAP4K3 (GLK) is a positive regulator of T-cell signaling and T-cell-mediated immune responses. MAP4K3 overexpression-induced RORγt–AhR complex specifically controls interleukin 17A (IL-17A) production in T cells, leading to autoimmune responses. Consistently, MAP4K3 and the RORγt–AhR complex are overexpressed in the T cells of human SLE patients, as are DUSP4 and DUSP23. In addition, DUSPs are also involved in either human autoimmune diseases (DUSP2, DUSP7, DUSP10, and DUSP12) or T-cell activation (DUSP1, DUSP5, and DUSP14). In this review, we summarize the MAP4Ks and DUSPs that are potential biomarkers and/or therapeutic targets for SLE.

Impaired T-cell activation in patients with systemic lupus erythematosus

1989 ◽  
Vol 9 (6) ◽  
pp. 469-476 ◽  
Author(s):  
Stanislaw Sierakowski ◽  
Eugene J. Kucharz ◽  
Robert W. Lightfoot ◽  
James S. Goodwin
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Systemic Lupus

Is there any correlation between high sensitive CRP and disease activity in systemic lupus erythematosus?

Lupus ◽  
2011 ◽  
Vol 20 (14) ◽  
pp. 1494-1500 ◽  
Author(s):  
Z Rezaieyazdi ◽  
M Sahebari ◽  
MR Hatef ◽  
B Abbasi ◽  
H Rafatpanah ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Hs Crp

The role of C-reactive protein (CRP) in systemic lupus erythematosus (SLE) as an inflammatory marker is still controversial. Recently, more sensitive methods, such as high sensitive CRP (hs-CRP) have been used to detect micro-inflammation. The role of hs-CRP in lupus flare has not been documented well. We conducted this study to examine the correlation between hs-CRP serum concentrations and disease activity in lupus. Ninety-two SLE patients and 49 healthy controls contributed to our study. Most confounding factors influencing the hs-CRP values were excluded. Disease activity was estimated using the SLE Disease Activity Index (SLEDAI-2K). hs-CRP values were determined using an enzyme-linked immunosorbent assay (ELISA) kit. Serum values of hs-CRP were significantly higher ( p < 0.001, z = 3.29) in patients compared with healthy controls. The cutoff point for hs-CRP between patients and controls was 0.93 mg/L (Youden’s Index = 0.39). There was no correlation between hs-CRP serum levels and disease activity. Furthermore, hs-CRP values did not correlate with any of the laboratory parameters, except for C3 ( p = 0.003, rs = −0.2) and C4 ( p = 0.02, rs = −0.1). Although hs-CRP serum levels were significantly higher in lupus patients compared with healthy controls, it seems that this marker is not a good indicator for disease activity.

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