scholarly journals Lymphocytes Tγδ in clinically normal skin and peripheral blood of patients with systemic lupus erythematosus and their correlation with disease activity

2001 ◽  
Vol 10 (4) ◽  
pp. 179-189 ◽  
Author(s):  
Ewa Robak ◽  
Hanna Niewiadomska ◽  
Tadeusz Robak ◽  
Jacek Bartkowiak ◽  
Jerzy Z. Bloński ◽  
...  

Human Tγσ lymphocytes constitute from 1 to 15% of all peripheral blood lymphocytes. Recent work has demonstrated that this population plays a major role in the pathogenesis of infectious and immune diseases. Increased numbers of γσ T cells have been found in affected skin from systemic sclerosis and chronic cutaneous lupus erythematosus patients.In our study, we have determined the numbers of Tγσ lymphocytes and their subpopulations in peripheral blood from 29 patients with systemic lupus erythematosus (SLE) and in 19 healthy volunteers using flow cytometry and specific monoclonal antibodies. The same cells in uninvolved skin from SLE patients and human controls using immunohistochemical analysis were estimated. T-Cell receptor (TCR) delta chain gene rearrangement was identified with primers for Vσ1, Vσ2 and Vσ3 by the polymerase chain reaction. Statistical analysis showed a significantly decreased number of γσ T cells in SLE patients (26.4 Ī 16.9/μl) compared with the control group (55.3 Ī 20.6/μl) (p<0.001). The number of Vσ2 TCR+ and Vγ9 TCR+ subpopulations was also lower in SLE patients than in healthy persons. No statistical correlation between disease activity and the number of γσ T cells was demonstrated. The percentage of T γσ lymphocytes in clinically normal skin from SLE patients was twice (22.0 Ī 9.4%) that found in the skin from healthy persons (11.1 Ī 5.5%) (p<0.002). Higher percentages of the Vσ2 TCR+ and Vγ9 TCR+ subpopulation of lymphocytes were found in the skin from SLE patients. We have also found positive correlation between the percentage of Tγσ lymphocytes in skin and the activity of SLE (r=0.594, p<0.001), and between subpopulation Vσ3 TCR+ and disease activity (r=0.659, p<0.001). In conclusion, the results of our studies demonstrate that, in patients with SLE, accumulation of Tγσ lymphocytes can be seen in clinically normal skin, and the percentage of these cells correlates with the activity of the disease.

2021 ◽  
Author(s):  
Wei Quan ◽  
Jingnan An ◽  
Gang Li ◽  
Guanghui Qian ◽  
Meifang Jin ◽  
...  

Abstract Background: Childhood-onset systemic lupus erythematosus (cSLE) is a kind of chronic inflammatory disease characterized by a highly abnormal immune system. This study aimed to detect expression of the Th cytokines IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ and TNF-α in the peripheral blood of children with cSLE; clinical symptoms; and a disease index and discuss the relationship between the Th cell cytokine regulatory network and onset of systemic lupus erythematosus (SLE) in children and disease outcome.Methods: A total of 33 children with cSLE and 30 healthy children were enrolled in this study. Children in the cSLE group were classified into the inactive cSLE group or active cSLE group according to their SLE disease activity index 2000 (SLEDAI-2K). Th cytokine profiles in peripheral blood of different groups were detected and analyzed.Results: The levels of IL-2, IL-10 and IL-21 in the cSLE group were significantly higher than those in the healthy control group (P < 0.05, P<0.01 and P<0.01, respectively). The expression of IL-2, IL-10 and IL-21 in the active cSLE group was significantly higher than that in the healthy control group (P<0.05, P<0.01 and P<0.05, respectively), but IL-22 expression was remarkably lower in the active cSLE group than in the healthy control group (P<0.001). IL-21 in the inactive SLE group was significantly higher than that in the healthy control group (P<0.05). The levels of IL-2 and IL-10 in the active cSLE group were significantly higher than those in the inactive cSLE group (P<0.01 and P<0.05). In-depth analysis showed that the expression levels of IL-2 (r=0.382, P=0.028), IL-6 (r=0.514, P=0.002) and IL-10 (r=0.429, P=0.016) were positively correlated with disease activity. Conclusion: This study provides a theoretical basis for the discovery of effective methods to regulate imbalance in T lymphocyte subsets in cSLE, which may open up potential new approaches for the diagnosis of cSLE.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1072.1-1072
Author(s):  
Y. J. Choi ◽  
E. K. Lee ◽  
M. S. Lee ◽  
C. H. Lee ◽  
C. H. Chung ◽  
...  

Background:Semaphorin has been found as a neuronal guidance molecule, but has recently been called “immune semaphorin”, as their critical role in immune cell activation, differentiation and migration has been revealed. In particular, class 4 semaphorin has been shown to contribute to lymphocyte activation and immune homeostasis.Objectives:This study was aimed to investigate the expression of neuropilin-1 (NRP-1), the receptor of class 4 semaphorin, in the murine mouse model of systemic lupus erythematosus (SLE) and the patients with SLE and the correlation between the expression of NRP-1 and disease activity of SLE.Methods:The expression of NRP-1 was measured in T cells in spleen and renal tissue in control mouse and TLR-7 agonist-induced lupus mouse by flow cytometry, PCR, and immunofluorescence (IF). CD4+ T cells from human peripheral blood were isolated to investigate the expression of NRP-1 in healthy control and the patients with SLE (n=40).Results:The frequency of NRP-1 positivity in CD4+ T cells in spleen was significantly higher in lupus mouse group (median [interquartile range]: 15.34 [14.84] %) compared to vehicle mouse group (4.0 [2.77]%). The quantitative analysis of fluorescense intensity in kidney stained for NRP-1 revealed the increased level in lupus group compared to vehicle group. The CD4+ T cells from peripheral blood mononuclear cells in the patients with lupus also showed significantly higher frequency of NRP-1 positive CD4+ T cells than those from healthy controls. Comparing the correlation of the expression of NRP-1 and disease activity with SLEDAI, C3, C4, and anti-DNA antibodies, the significant correlation between NRP-1 and disease activity markers were confirmed.Conclusion:Our results demonstrate that higher expression of NRP-1 in CD4+ T cells and its significant correlation with disease activity of SLE. These results indicate that pathologic contribution of NRP-1 in the pathogenesis of SLE and potential of targeting NRP-1 for the treatment of SLE.References:[1]Nishide M, Kumanogoh A. The role of semaphorins in immune responses and autoimmune rheumatic diseases. Nat Rev Rheumatol. 2018 Jan;14(1):19-31.Disclosure of Interests:None declared


Lupus ◽  
2022 ◽  
pp. 096120332110664
Author(s):  
Chanidapa Wongtada ◽  
Stephen J Kerr ◽  
Pawinee Rerknimitr

Background The lupus band test (LBT) using a sample of clinically normal skin was proposed as a useful diagnostic test for systemic lupus erythematosus (SLE). It is mostly performed to help diagnosing SLE in patients with insufficient clinical and serological profiles. However, most published studies on its utility are outdated and the results remain controversial. Objectives To determine the diagnostic performance of LBT on non-lesion sun-protected (NLSP) and sun-exposed (NLSE) skin for SLE. Methods Consecutively presenting patients with clinical and serological suspicion of SLE who had LBT performed on non-lesion skin during January 2012 to August 2021 were retrospectively studied. LBT performed on either NLSE or NLSP skin biopsies were all included. Laboratory characteristics, number, types and patterns of deposited immunoreactants and disease activity were also assessed. Results LBT was performed in 57 patients with suspected SLE. LBT was positive in 18/57, 9/28 and 6/21 patients in overall non-lesion, NLSE and NLSP, respectively. Of all patients, 23 patients were diagnosed with SLE and 34 patients with other diseases. Overall, the sensitivity and specificity of LBT on non-lesion skin was 56.5% and 88.2%, respectively. The ability of the test to discriminate between those with and without SLE, assessed by the area under the Receiver-Operating Characteristic curve, was 0.72 (0.61–0.84). The sensitivity and specificity of LBT on NLSE skin was 58.3% and 87.5% while those of NLSP skin, were 57.1% and 85.7%, respectively. We found no significant correlation between the positivity of LBT and overall disease activity. Types, number and pattern of deposited immunoreactants also showed no correlation with disease activity (all p > 0.05). Conclusions Used as a diagnostic adjunct, non-lesion LBT is still of value for diagnosing SLE in inconclusive cases.


Lupus ◽  
2020 ◽  
Vol 29 (2) ◽  
pp. 182-190
Author(s):  
W Batista Cicarini ◽  
R C Figueiredo Duarte ◽  
K Silvestre Ferreira ◽  
C de Mello Gomes Loures ◽  
R Vargas Consoli ◽  
...  

We have explored the relationship between possible hemostatic changes and clinical manifestation of the systemic lupus erythematosus (SLE) as a function of greater or lesser disease activity according to Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) criteria. Endothelial injury and hypercoagulability were investigated in patients with SLE by measuring thrombomodulin (TM), D-dimer (DDi) and thrombin generation (TG) potential. A total of 90 participants were distributed into three groups: 1) women with SLE presenting with low disease activity (laSLE) (SLEDAI-2K ≤ 4), 2) women with SLE presenting with moderate to high disease activity (mhaSLE) (SLEDAI-2K > 4), and 3) a control group comprising healthy women. Levels of TM and DDi were higher both in the laSLE and mhaSLE groups compared to controls and in mhaSLE compared to the laSLE group. With respect to TG assay, lagtime and endogen thrombin potential, low concentrations of tissue factor provided the best results for discrimination among groups. Analysis of these data allow us to conclude that TM, DDi and TG are potentially useful markers for discriminating patients with very active from those with lower active disease. Higher SLE activity may cause endothelial injury, resulting in higher TG and consequently a hypercoagulability state underlying the picture of thrombosis common in this inflammatory disease.


Lupus ◽  
2021 ◽  
pp. 096120332110345
Author(s):  
Stefan Vordenbäumen ◽  
Alexander Sokolowski ◽  
Anna Rosenbaum ◽  
Claudia Gebhard ◽  
Johanna Raithel ◽  
...  

Objective Hypomethylation of CD40-ligand (CD40L) in T-cells is associated with increased disease activity in systemic lupus erythematosus (SLE). We therefore investigated possible associations of dietary methyl donors and products with CD40L methylation status in SLE. Methods Food frequency questionnaires were employed to calculate methyl donor micronutrients in 61 female SLE patients (age 45.7 ± 12.0 years, disease duration 16.2 ± 8.4 years) and compared to methylation levels of previously identified key DNA methylation sites (CpG17 and CpG22) within CD40L promotor of T-cells using quantitative DNA methylation analysis on the EpiTYPER mass spectrometry platform. Disease activity was assessed by SLE Disease Activity Index (SLEDAI). Linear regression modelling was used. P values were adjusted according to Benjamini & Hochberg. Results Amongst the micronutrients assessed (g per day), methionine and cysteine were associated with methylation of CpG17 (β = 5.0 (95%CI: 0.6-9.4), p = 0.04; and β = 2.4 (0.6-4.1), p = 0.02, respectively). Methionine, choline, and cysteine were additionally associated with the mean methylation of the entire CD40L (β = 9.5 (1.0-18.0), p = 0.04; β = 1.6 (0.4-3.0), p = 0.04; and β = 4.3 (0.9-7.7), p = 0.02, respectively). Associations of the SLEDAI with hypomethylation were confirmed for CpG17 (β=-32.6 (-60.6 to -4.6), p = 0.04) and CpG22 (β=-38.3 (-61.2 to -15.4), p = 0.004), but not the mean methylation of CD40L. Dietary products with the highest impact on methylation included meat, ice cream, white bread, and cooked potatoes. Conclusions Dietary methyl donors may influence DNA methylation levels and thereby disease activity in SLE.


2019 ◽  
Vol 41 (3) ◽  
pp. 209-214 ◽  
Author(s):  
Maha Bassiouny ◽  
Ahmed Sonbol ◽  
Hend Eissa ◽  
Amira El-Shanawany ◽  
Alaa Labeeb

Lupus ◽  
2018 ◽  
Vol 27 (13) ◽  
pp. 2057-2068 ◽  
Author(s):  
Z-J Yin ◽  
B-M Ju ◽  
L Zhu ◽  
N Hu ◽  
J Luo ◽  
...  

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.


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