scholarly journals CCR6+ Th cell distribution differentiates systemic lupus erythematosus patients based on anti-dsDNA antibody status

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4294 ◽  
Author(s):  
Wei Zhong ◽  
Zhenyu Jiang ◽  
Jiang Wu ◽  
Yanfang Jiang ◽  
Ling Zhao
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Th2 Cells ◽  
Systemic Lupus ◽  
Th Cells ◽  
Clinical Indicators ◽  
Th Cell ◽  
Dsdna Antibody ◽  
Treatment Naïve

Background Systemic lupus erythematosus (SLE) disease has been shown to be associated with the generation of multiple auto-antibodies. Among these, anti-dsDNA antibodies (anti-DNAs) are specific and play a pathogenic role in SLE. Indeed, anti-DNA+ SLE patients display a worse disease course. The generation of these pathogenic anti-DNAs has been attributed to the interaction between aberrant T helper (Th) cells and autoimmune B cells. Thus, in this study we have investigated whether CCR6+Th cells have the ability to differentiate SLE patients based on anti-DNA status, and if their distribution has any correlation with disease activity. Methods We recruited 25 anti-DNA+ and 25 anti-DNA− treatment-naive onset SLE patients, matched for various clinical characteristics in our nested matched case-control study. CCR6+ Th cells and their additional subsets were analyzed in each patient by flow cytometry. Results Anti-DNA+ SLE patients specifically had a higher percentage of Th cells expressing CCR6 and CXCR3. Further analysis of CCR6+ Th cell subsets showed that anti-DNA+ SLE patients had elevated proportions of Th9, Th17, Th17.1 and CCR4/CXCR3 double-negative (DN) cells. However, the proportions of CCR6− Th subsets, including Th1 and Th2 cells, did not show any association with anti-DNA status. Finally, we identified a correlation between CCR6+ Th subsets and clinical indicators, specifically in anti-DNA+ SLE patients. Conclusions Our data indicated that CCR6+ Th cells and their subsets were elevated and correlated with disease activity in anti-DNA+ SLE patients. We speculated that CCR6+ Th cells may contribute to distinct disease severity in anti-DNA+ SLE patients.

scholarly journals The expansion of activated naive DNA autoreactive B cells and its association with disease activity in systemic lupus erythematosus patients

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Kittikorn Wangriatisak ◽  
Chokchai Thanadetsuntorn ◽  
Thamonwan Krittayapoositpot ◽  
Chaniya Leepiyasakulchai ◽  
Thanitta Suangtamai ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Disease Activity ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Autoreactive B Cells ◽  
Dsdna Antibody ◽  
Cell Subpopulations ◽  
B Cell Subsets

Abstract Background Autoreactive B cells are well recognized as key participants in the pathogenesis of systemic lupus erythematosus (SLE). However, elucidating the particular subset of B cells in producing anti-dsDNA antibodies is limited due to their B cell heterogeneity. This study aimed to identify peripheral B cell subpopulations that display autoreactivity to DNA and contribute to lupus pathogenesis. Methods Flow cytometry was used to detect total B cell subsets (n = 20) and DNA autoreactive B cells (n = 15) in SLE patients’ peripheral blood. Clinical disease activities were assessed in SLE patients using modified SLEDAI-2 K and used for correlation analyses with expanded B cell subsets and DNA autoreactive B cells. Results The increases of circulating double negative 2 (DN2) and activated naïve (aNAV) B cells were significantly observed in SLE patients. Expanded B cell subsets and DNA autoreactive B cells represented a high proportion of aNAV B cells with overexpression of CD69 and CD86. The frequencies of aNAV B cells in total B cell populations were significantly correlated with modified SLEDAI-2 K scores. Further analysis showed that expansion of aNAV DNA autoreactive B cells was more related to disease activity and serum anti-dsDNA antibody levels than to total aNAV B cells. Conclusion Our study demonstrated an expansion of aNAV B cells in SLE patients. The association between the frequency of aNAV B cells and disease activity patients suggested that these expanded B cells may play a role in SLE pathogenesis.

Increased CD4+CD25-Foxp3+ T cells in Chinese systemic lupus erythematosus: correlate with disease activity and organ involvement

Lupus ◽  
2018 ◽  
Vol 27 (13) ◽  
pp. 2057-2068 ◽  
Author(s):  
Z-J Yin ◽  
B-M Ju ◽  
L Zhu ◽  
N Hu ◽  
J Luo ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Cell Subset ◽  
Treg Cells ◽  
Organ Involvement ◽  
Systemic Lupus ◽  
Clinical Indicators ◽  
Disease States

Objective The increment of CD4+CD25−Foxp3+T cells has been reported in systemic lupus erythematosus (SLE) patients. However, the exact identity of this T cell subset is still unclear. Thus, we analyzed CD4+CD25−Foxp3+T cells and Treg cells (CD4+CD25+Foxp3+ T cells) in a large sample of Chinese SLE patients in different disease states. Methods A total of 280 SLE patients and 38 healthy volunteers were enrolled, which included 21 patients with untreated new-onset lupus (UNOL), 13 patients with drug withdrawal more than 6 months and 246 patients with treatments. Phenotypic and functional analysis of peripheral blood CD4+CD25−Foxp3+ T cells and Treg cells were performed by flow cytometry. The correlation of CD4+CD25−Foxp3+T cells and Treg cells with disease activity, clinical indicators and organ involvement were analyzed. Results CD4+CD25−Foxp3+ T cells and Treg cells were significantly increased in SLE patients and showed significantly positive correlations with disease activity. CD4+CD25−Foxp3+ T cells were significantly increased in patients with skin and hematologic involvement as well as arthritis. Diverse changes between CD4+CD25−Foxp3+ T cells and Treg cells when faced with different medications, especially HCQ and MMF. CD4+CD25−Foxp3+ T cells expressed more IFN-γ and less CTLA-4 than CD4+CD25+Foxp3+ T cells, which were similar to CD4+CD25+Foxp3− T cells, and expressed similar IL-17, ICOS and Helios to CD4+CD25+Foxp3+ T cells. The synthesis capacity of IL-10 of CD4+CD25−Foxp3+ T cells and the expression of GITR on CD4+CD25−Foxp3+ T cells were between CD4+CD25+Foxp3+ and CD4+CD25+Foxp3− T cells. Conclusions Our results indicate that increased CD4+CD25−Foxp3+ T cells in lupus patients, which combined the features of suppression and pro-inflammatory, may serve as a biomarker for disease activity and organ involvement in SLE.

scholarly journals Polymorphisms of MFGE8 are associated with susceptibility and clinical manifestations through gene expression modulation in Koreans with systemic lupus erythematosus

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Wook-Young Baek ◽  
Ji-Min Woo ◽  
Hyoun-Ah Kim ◽  
Ju-Yang Jung ◽  
Chang-Hee Suh
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Milk Fat ◽  
Clinical Manifestations ◽  
Αvβ3 Integrin ◽  
Apoptotic Cells ◽  
Systemic Lupus ◽  
Dsdna Antibody

AbstractSystemic lupus erythematosus (SLE) is characterized by impaired clearance of apoptotic cells. Milk fat globule epidermal growth factor 8 (MFGE8) is a protein that connects αvβ3 integrin on phagocytic macrophages with phosphatidylserine on apoptotic cells. We investigated whether genetic variation of the MFGE8 gene and serum MFGE8 concentration are associated with SLE. Single nucleotide polymorphisms (SNPs) were genotyped and serum concentrations were analyzed. The rs2271715 C allele and rs3743388 G allele showed higher frequency in SLE than in healthy subjects (HSs). Three haplotypes were found among 4 SNPs (rs4945, rs1878327, rs2271715, and rs3743388): AACG, CGCG, and CGTC. CGCG haplotype was significantly more common in SLE than in HSs. rs4945 was associated with the erythrocyte sedimentation rate and rs1878327 was associated with alopecia, C-reactive protein, complement 3, anti-dsDNA antibody, and high disease activity. rs2271715 and rs3743388 were associated with renal disease, cumulative glucocorticoid dose, and cyclophosphamide and mycophenolate mofetil use. Serum MFGE8 concentrations were significantly higher in SLE than in HSs. Furthermore, the levels of MFGE8 were significantly higher in SLE than HSs of the rs2271715 CC genotype. In conclusion, MFGE8 genetic polymorphisms are associated not only with susceptibility to SLE but also with disease activity through modulation of gene expression.

Clinical evaluation of total and high-avidity anti-dsDNA antibody assays for the diagnosis of systemic lupus erythematosus

Lupus ◽  
2019 ◽  
Vol 28 (12) ◽  
pp. 1387-1396 ◽  
Author(s):  
W Yuan ◽  
H Cao ◽  
P Wan ◽  
R Shi ◽  
S Zhou ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Superior Performance ◽  
High Avidity ◽  
Systemic Lupus ◽  
Dsdna Antibody ◽  
In Vitro Diagnostic

Background This study evaluated the diagnostic performances of total and high-avidity (HA) anti-dsDNA enzyme immunoassays (EIA) in Chinese systemic lupus erythematosus (SLE) patients. Methods A total of 410 serum samples from 217 SLE patients, 54 patients with other systemic autoimmune diseases, and 139 healthy subjects were tested on total and HA anti-dsDNA EIA, as well as three commercial in vitro diagnostic kits: BioPlex 2200 ANA Screen, Kallestad anti-dsDNA EIA, and Crithidia Lucilae IFA. The disease activities of SLE patients were assessed using the modified SLE Disease Activity Index. The diagnostic performances of each assay were analyzed using Analyse-it software. Results The diagnostic performances of the total and HA anti-dsDNA EIA kits were comparable to other commercially available in vitro diagnostic assays. Receiver operating characteristic curve analysis demonstrated an area under the curve ranging from 0.85 to 0.89, with the total anti-dsDNA kit demonstrating the highest sensitivity and the HA kit showing higher specificity. An overall agreement of >90% was observed between the total and HA anti-dsDNA EIA kits and commercially available quantitative anti-dsDNA kits. The ratio of HA to total anti-dsDNA antibody was significantly higher among SLE patients with active disease status and/or kidney damage. All assays exhibited a significant correlation with disease activity and multiple clinical manifestations. Conclusions While the clinical performances of various anti-dsDNA assays showed adequate agreements, the BioPlex 2200 anti-dsDNA assay demonstrated the highest positive likelihood ratio and odds ratio. The HA anti-dsDNA EIA kit in association with the total anti-dsDNA kit provided superior performance in SLE diagnosis and monitoring disease activity.

Galectin-9 is an easy to measure biomarker for the interferon signature in systemic lupus erythematosus and antiphospholipid syndrome

2018 ◽  
Vol 77 (12) ◽  
pp. 1810-1814 ◽  
Author(s):  
Lucas L van den Hoogen ◽  
Joël A G van Roon ◽  
Jorre S Mertens ◽  
Judith Wienke ◽  
Ana Pinheiro Lopes ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Complement C3 ◽  
Tumour Necrosis Factor Receptor ◽  
Systemic Lupus ◽  
Dsdna Antibody

ObjectiveThe interferon (IFN) signature is related to disease activity and vascular disease in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) and represents a promising therapeutic target. Quantification of the IFN signature is currently performed by gene expression analysis, limiting its current applicability in clinical practice. Therefore, the objective of this study was to establish an easy to measure biomarker for the IFN signature.MethodsSerum levels of galectin-9, CXCL-10 (IP-10) and tumour necrosis factor receptor type II (TNF-RII) were measured in patients with SLE, SLE+APS and primary APS (PAPS) and healthy controls (n=148) after an initial screening of serum analytes in a smaller cohort (n=43). Analytes were correlated to measures of disease activity and the IFN signature. The performance of galectin-9, CXCL-10 and TNF-RII as biomarkers to detect the IFN signature was assessed by receiver operating characteristic curves.ResultsGalectin-9, CXCL-10 and TNF-RII were elevated in patients with SLE, SLE+APS and PAPS (p<0.05) and correlated with disease activity and tissue factor expression. Galectin-9 correlated stronger than CXCL-10 or TNF-RII with the IFN score (r=0.70, p<0.001) and was superior to CXCL-10 or TNF-RII in detecting the IFN signature (area under the curve (AUC) 0.86). Importantly, in patients with SLE(±APS), galectin-9 was also superior to anti-dsDNA antibody (AUC 0.70), or complement C3 (AUC 0.70) and C4 (AUC 0.78) levels in detecting the IFN signature.ConclusionGalectin-9 is a novel, easy to measure hence clinically applicable biomarker to detect the IFN signature in patients with systemic autoimmune diseases such as SLE and APS.

scholarly journals Association of Elevated Serum Soluble Cd226 Levels With the Disease Activity and Flares of Systemic Lupus Erythematosus

2021 ◽  
Author(s):  
Miki Nakano ◽  
Masahiro Ayano ◽  
Kazuo Kushimoto ◽  
Shotaro Kawano ◽  
Kazuhiko Higashioka ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Laboratory Data ◽  
Elevated Serum ◽  
Soluble Form ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cumulative Probability ◽  
Systemic Lupus ◽  
Dsdna Antibody

Abstract Background: CD226 is an activating receptor expressed on the cell surface of natural killer cells and T cells. A soluble form of CD226 (sCD226) is known to be shed from the membrane type of CD226 (mCD226). Although CD226 polymorphism and mCD226 are known to be involved in systemic lupus erythematosus (SLE), the involvement of sCD226 in SLE is still unknown. Therefore, we aimed to reveal the association of sCD226 with SLE.Methods: We measured serum sCD226 levels using an enzyme-linked immunosorbent assay in 58 SLE patients and 33 healthy controls (HCs) and evaluated their associations with SLE Disease Activity Index 2000 (SLEDAI-2K), clinical manifestations, and laboratory data. We defined the maximum values of sCD226 in HCs as a cut-off level and compared the cumulative probability of flare for patients with high and low sCD226 levels. Results: Serum sCD226 levels showed no significant differences between SLE patients and HCs. However, sCD226 levels were significantly elevated in active SLE patients with a SLEDAI-2K score of ≥20 compared with HCs. In SLE patients, sCD226 levels were significantly correlated with SLEDAI-2K scores and anti-dsDNA antibody titers. Moreover, the cumulative probability of flare was markedly higher in patients with high sCD226 than in those with low sCD226. In patients with neuropsychiatric involvement, sCD226 levels were elevated and reflected neuropsychiatric disease activity. Conclusion: Serum sCD226 levels were associated with disease activity and flares of SLE. Thus, it may be a useful biomarker for SLE, and its monitoring allows for more precise SLE management.

scholarly journals Association of elevated serum soluble CD226 levels with the disease activity and flares of systemic lupus erythematosus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Miki Nakano ◽  
Masahiro Ayano ◽  
Kazuo Kushimoto ◽  
Shotaro Kawano ◽  
Kazuhiko Higashioka ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Laboratory Data ◽  
Elevated Serum ◽  
Clinical Manifestations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cumulative Probability ◽  
Systemic Lupus ◽  
Dsdna Antibody

AbstractCD226 is an activating receptor expressed on the cell surface of natural killer cells and T cells. Although CD226 polymorphism is known to be involved in systemic lupus erythematosus (SLE), the involvement of soluble CD226 (sCD226) in SLE is still unknown. In the present study, we measured serum sCD226 levels using an enzyme-linked immunosorbent assay in 58 SLE patients and 33 healthy controls (HCs) and evaluated their associations with SLE Disease Activity Index 2000 (SLEDAI-2K), clinical manifestations, laboratory data, and the cumulative probability of flare. Serum sCD226 levels showed no significant differences between SLE patients and HCs. However, sCD226 levels were significantly elevated in active SLE patients with a SLEDAI-2K score of ≥ 20 compared with HCs. In SLE patients, sCD226 levels were significantly correlated with SLEDAI-2K scores and anti-dsDNA antibody titers. Moreover, the cumulative probability of flare was markedly higher in patients with high sCD226 than in those with low sCD226. In patients with neuropsychiatric involvement, sCD226 levels were elevated and reflected neuropsychiatric disease activity. These findings indicate that serum sCD226 levels are associated with disease activity and flares of SLE. Thus, it may be a useful biomarker for SLE, and its monitoring allows for more precise SLE management.

scholarly journals Correlation of Circulating Glucocorticoid-Induced TNFR-Related Protein Ligand Levels with Disease Activity in Patients with Systemic Lupus Erythematosus

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Lei Gu ◽  
Lingxiao Xu ◽  
Xiaojun Zhang ◽  
Wenfeng Tan ◽  
Hong Wang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Renal Involvement ◽  
Clinical Manifestations ◽  
Inactive Disease ◽  
Healthy Controls ◽  
Related Protein ◽  
Systemic Lupus ◽  
Dsdna Antibody

The aim of this paper is to investigate the correlation of glucocorticoid-induced tumor necrosis factor receptor- (TNFR-) related protein ligand (GITRL) with disease activity and organ involvement in patients with systemic lupus erythematosus (SLE). Serum GITRL levels were measured in 58 patients with SLE and 30 healthy controls matched for age and sex. Patients were assessed for clinical and laboratory variables. Correlations of serum GITRL levels with SLEDAI, laboratory values, and clinical manifestations were assessed. Serum GITRL levels were determined by ELISA. Serum GITRL levels were markedly increased in patients with SLE compared with healthy controls (mean 401.3 ng/mL and 36.59 ng/mL, resp.;P<0.0001). SLE patients with active disease showed higher serum GITRL levels compared to those with inactive disease (mean 403.3 ng/mL and 136.3 ng/mL, resp;P=0.0043) as well as normal controls (36.59 ng/mL;P<0.0001). Serum GITRL levels were positively correlated with SLEDAI, titers of anti-dsDNA antibody, erythrocyte sedimentation rate (ESR), and IgM and negatively correlated with complement3 (C3). Serum GITRL levels were higher in SLE patients with renal involvement and vasculitis compared with patients without the above-mentioned manifestations.

scholarly journals Increased Proportion of CD226+ B Cells Is Associated With the Disease Activity and Prognosis of Systemic Lupus Erythematosus

2021 ◽  
Vol 12 ◽  
Author(s):  
Miki Nakano ◽  
Masahiro Ayano ◽  
Kazuo Kushimoto ◽  
Shotaro Kawano ◽  
Kazuhiko Higashioka ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Renal Involvement ◽  
Laboratory Data ◽  
Clinical Manifestations ◽  
Systemic Lupus ◽  
Dsdna Antibody

BackgroundCD226, an activating receptor expressed on the surface of natural killer (NK) cells and T cells, is also seen on B cells and CD226 polymorphism is associated with systemic lupus erythematosus (SLE). Because the specific roles of CD226+ B cells in SLE are still unknown, we investigated the association of CD226+ B cells with SLE.MethodsWe measured CD226 expression on B cells and its subsets using flow cytometry in 48 SLE patients and 24 healthy controls (HCs). We assessed the relationships between CD226+ B cells and SLE Disease Activity Index 2000 (SLEDAI-2K), clinical manifestations, laboratory data, and prognosis after 12 months.ResultsThe proportions of CD226+ cells in whole B cells and all its subsets were significantly higher in SLE patients than HCs. In SLE patients, the proportions of CD226+ B cells and CD226+ switched-memory (SM) B cells were significantly correlated with SLEDAI-2K scores and anti-dsDNA antibody titers, and negatively correlated with serum complement levels. Moreover, basal percentages of CD226+ B cells and CD226+ SM B cells were low in patients who were in Lupus Low Disease Activity State after 12 months. In patients with renal involvement, the proportion of CD226+ B cells increased. Additionally, the proportion of CD226+ B cells was higher in patients who were not in complete renal remission after 12 months.ConclusionsIncreased proportion of CD226+ B cells was associated with disease activity and prognosis of SLE. CD226+ B cells may be a useful biomarker for the management of SLE.

Sandplay therapy could be a method to decrease disease activity and psychological stress in children with systemic lupus erythematosus

Lupus ◽  
2022 ◽  
pp. 096120332110723
Author(s):  
Jinjiao Li ◽  
Yanjun Shi ◽  
Wei Zhou
Keyword(s):  
Mental Health ◽  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Emotional Health ◽  
Initial Diagnosis ◽  
Systemic Lupus ◽  
Sandplay Therapy ◽  
Clinical Indicators ◽  
Wide Range

Objective Although the prevalence rate of childhood-onset systemic lupus erythematosus (cSLE) is far lower than that of adults, cSLE has a high rate of organ involvement, rapid development and poor prognosis, which is more serious than that in adults. And studies have shown that a wide range of physiological, functional, nerve, and organ damage will have a great impact on the mental health of children. At present, there is no relevant psychological intervention research for cSLE in China. This paper aimed to explore the effect of Sandplay therapy on mental health and disease activity of children with cSLE. Methods Forty childrens with cSLE were randomly divided into control group (CG) and intervention group (IG); the CG were treated with glucocorticoid, immunosuppressant and other drugs, while the IG were treated with Sandplay therapy in addition to drug therapy, at the time of 0, 2, and 4 weeks after initial diagnosis, respectively. The questionnaire evaluation and related clinical indicators of the two groups were compared and analyzed (before psychotherapy intervention) at 0, 2, 4, and 12 weeks after initial diagnosis. Results There was no significant difference between the two groups in the evaluation of questionnaire and related clinical indicators at the time 0, 2 weeks after initial diagnosis respectively. At 12 weeks after the intervention, the score of Short version of the Children’s Depression Inventory (CDI-S) in the IG was significantly lower than that in the CG, the score of The Screen for Child Anxiety Related Emotional Disorders (SCARED) scale in the IG was significantly lower than that in the CG, and the Pediatric Quality of Life Inventory (PedsQL 4.0) showed that the scores of social function, school performance, and emotional health of the IG were higher than those of the CG ( p < 0.05), and the clinical indexes of the IG were better than those of the CG ( p < 0.05). Conclusion Sandplay therapy may help to slow down the occurrence and development of anxiety and depression and reduce disease activity in patients with cSLE.

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