scholarly journals OP0307 GUT MICROBIOTA AND ITS RELEVANCE TO PERIPHERAL LYMPHOCYTE SUBPOPULATION IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 188-189
Author(s):  
T. Cheng ◽  
X. Wang ◽  
S. X. Zhang ◽  
J. Yang ◽  
C. Zhao ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Gut Microbiota ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Lymphocyte Subsets ◽  
Treg Cells ◽  
Peripheral Lymphocyte ◽  
Lymphocyte Subpopulations ◽  
Systemic Lupus ◽  
T Lymphocyte Subsets

Background:Systemic lupus erythematosus (SLE) is an autoimmune disease with disturbance of lymphocyte subpopulations1. Growing experimental and clinical evidence suggests that chronic inflammatory response induced by gut microbiome critically contribute to the development of SLE2 3.Objectives:To investigate the characteristics of gut microbiome and the associations between flora and peripheral lymphocyte subpopulations in SLE patients.Methods:A total of 19 SLE patients who fulfilled the 2019 American college of Rheumatology (ACR) and European League Against Rheumatism (EULAR) classification criteria and 16 age- and sex- matched healthy controls (HC) were enrolled in this study. The peripheral T lymphocyte subsets of these participants were assessed by flow cytometry and the gut microbiota were investigated via 16s rRNA. Indicators of disease activity such as erythrocyte sedimentation rate (ESR), complement C3 and C4 were recorded at the same time. Mann-Whitney U test was applied to compare T lymphocyte subsets between SLE patients and HC. Spearman analysis was used for calculating correlation between T subsets and highly expressed differential flora as well as their correlation with disease activity indicators. All P-values reported herein were two-tailed and P-value<0.05 was taken as statistically significant.Results:SLE patients had higher proportions of Th17 cells (P=0.020) and γδT cells (P=0.018) but lower levels of Treg cells (P=0.001), Tfh cells (P=0.018) and Naïve CD4+T cells (P=0.004) (Figure 1a-e). The diversity and relative abundance of intestinal flora in patients with SLE were significantly different from those in HCs. Detailly, the α-diversity was decreased in SLE (P<0.05) (Figure 2a-c). Compared with HC, 11 species of flora were discovered to be distinctly different(P<0.05) (Figure 2d-e). Moreover, there was a significant positive correlation between Treg levels and Ruminococcus2 (P=0.042), Th17 and Megamonas (P=0.009), γδT and Streptococcus (P=0.004) as well as Megamonas (P=0.003), Tfh and Bacteroides (P=0.040). Whereas Th1 levels and Bifidobacterium were negatively correlated in these participants (P=0.005). As for clinical disease measures, there were negative correlations not only between ESR and Treg cells (P=0.031) but also C4 and the amount of Unclassified Ruminococcaceae (P=0.032).Conclusion:Abnormality of T cell subsets, especially the level of Naïve CD4+T, γδT, Tfh, Treg, and Th17 cells contributes to the occurrence and progression of SLE, which may be related to the disturbance of gut microbiota. Therefore it is necessary to attach importance to the alteration of gut microbiota to prevent the outbreak of inflammation and maybe they can be identified as biomarkers predicting disease activity.References:[1]Katsuyama T, Tsokos GC, Moulton VR. Aberrant T Cell Signaling and Subsets in Systemic Lupus Erythematosus. Front Immunol 2018;9:1088. doi: 10.3389/fimmu.2018.01088 [published Online First: 2018/06/06][2]López P, de Paz B, Rodríguez-Carrio J, et al. Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients. Sci Rep 2016;6:24072. doi: 10.1038/srep24072 [published Online First: 2016/04/06][3]Esmaeili SA, Mahmoudi M, Momtazi AA, et al. Tolerogenic probiotics: potential immunoregulators in Systemic Lupus Erythematosus. J Cell Physiol 2017;232(8):1994-2007. doi: 10.1002/jcp.25748 [published Online First: 2016/12/21]Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared.

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.

Levels of Transforming Growth Factor-β Are Low in Systemic Lupus Erythematosus Patients with Active Disease

2010 ◽  
Vol 37 (10) ◽  
pp. 2039-2045 ◽  
Author(s):  
ANDREA BECKER-MEROK ◽  
GRO ØSTLI EILERTSEN ◽  
JOHANNES C. NOSSENT
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Growth Factor ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Transforming Growth Factor ◽  
Lymphocyte Subsets ◽  
Concomitant Treatment ◽  
Systemic Lupus ◽  
Cell Counts ◽  
Tgf Β1

Objective.Cytokines are central regulators of the immune response but the workings of this complex network in systemic lupus erythematosus (SLE) are not fully understood. We investigated a range of inflammatory and immune-modulating cytokines to determine their value as biomarkers for disease subsets in SLE.Methods.This was a cross-sectional study in 102 patients with SLE (87% women, disease duration 10.6 yrs). Circulating concentrations of interleukin 1β (IL-1β), IL-4, IL-6, IL-10, IL-12, IL-17, monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1 (MIP-1α), MIP-1β, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and total transforming growth factor-β1 (TGF-β1) were related to disease activity (SLE Disease Activity Index; SLEDAI), lymphocyte subsets, autoantibody levels, accrued damage (Systemic Lupus International Collaborating Clinics/ACR Damage Index; SDI), and concomitant treatment.Results.Patients with SLE had lower levels of TGF-β1 (p = 0.01) and IL-1β (p = 0.0004) compared to controls. TGF-β1 levels were lower in patients with SLEDAI scores 1–10 and SDI > 3; and were correlated with CD4+, CD8+, and natural killer cell counts; and were independent of steroid or cytotoxic drug use. Treatment with cardiovascular drugs was associated with lower IL-12 levels. No consistent disease associations existed for the other cytokines investigated.Conclusion.Lower TGF-β1 was the most consistent cytokine abnormality in patients with SLE. The associations with disease activity, lymphocyte subsets, and damage suggest that TGF-β1 may be a therapeutic target of interest in SLE.

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&lt;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&lt;0.05) by genes highly correlated with IL6ST expression (n=92 genes; r&gt;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 CD4+CD45RA−FOXP3low Regulatory T Cells as Potential Biomarkers of Disease Activity in Systemic Lupus Erythematosus Brazilian Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Helena L. Silva-Neta ◽  
Maria C. A. Brelaz-de-Castro ◽  
Mardonny B. O. Chagas ◽  
Henrique A. Mariz ◽  
Rodrigo G. de Arruda ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Linear Regression ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Foxp3 Expression ◽  
Treg Cells ◽  
Systemic Lupus ◽  
Peripheral Blood Mononuclear ◽  
Potential Biomarkers

Heren, we analyzed Treg cells as potential biomarkers of disease activity in systemic lupus erythematosus (SLE) patients. Peripheral blood mononuclear cells from 30 SLE patients (15 active: SLEDAI > 6/15 SLE remission: SLEDAI< 6) and 15 healthy volunteers were purified. Treg immunophenotyping was performed using CD4, CD25, CD45, CD127, and FOXP3 markers. CD4+FOXP3+ Treg activation state was investigated based on CD45RA and FOXP3 expression. To increase the accuracy of our findings, a multivariate linear regression was performed. We showed a significant increase in the frequency of CD4+FOXP3+ Treg cells in SLE patients. However, unlike all other Treg cells phenotypes analyzed, only eTreg (CD4+FOXP3highCD45RA-) (p=0.01) subtype was inversely correlated with disease activity while Foxp3+nontreg (CD4+FOXP3lowCD45RA-) (p=0.003) exerted a direct influence in the outcome of the disease. Foxp3+nontreg cells were the most consistent SLE active indicator, confirmed by multiple linear regression analyses. In summary, our results demonstrate Foxp3+nontreg cells as new biomarkers in the search of an effective therapeutic strategy in SLE.

scholarly journals Altered Profile of Fecal Microbiota in Newly Diagnosed Systemic Lupus Erythematosus Egyptian Patients

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Marian A. Gerges ◽  
Noura E. Esmaeel ◽  
Wafaa K. Makram ◽  
Doaa M. Sharaf ◽  
Manar G. Gebriel
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Gut Microbiota ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Healthy Subjects ◽  
Fecal Microbiota ◽  
Healthy Controls ◽  
Newly Diagnosed ◽  
Systemic Lupus ◽  
Egyptian Patients

Background. Dysbiosis of gut microbiota could promote autoimmune disorders including systemic lupus erythematosus (SLE). Clarifying this point would be of great importance in understanding the pathogenesis and hence the development of new strategies for SLE treatment. Aim. This study aimed to determine the fecal microbiota profile in newly diagnosed SLE patients compared to healthy subjects and to investigate the correlation of this profile with disease activity. Methods. Newly diagnosed SLE patients who fulfilled at least four of the American College of Rheumatology (ACR) criteria were enrolled during the study period. Patients with lupus were matched to healthy subjects. SLE activity was evaluated using the Systemic Lupus Disease Activity Index (SLEDAI-2K). Fresh fecal samples were collected from each subject. Genomic DNA was extracted from fecal samples. Quantitative real-time PCR was applied for quantitation of Firmicutes phylum, Bacteroidetes phylum, and Lactobacillus genus in comparison to the total fecal microbiota. Results of patients’ samples were compared to those of healthy subjects and were correlated to patients’ SLEDAI-2K score. Results. Twenty SLE patients’ samples were compared with 20 control samples. There was a significant alteration in SLE patients’ gut microbiota. A significantly lower ( p ≤ 0.001 ) Firmicutes/Bacteroidetes (F/B) ratio in SLE patients (mean ratio: 0.66%) compared to healthy subjects (mean ratio: 1.79%) was found. Lactobacillus showed a significant decrease in SLE patients ( p = 0.006 ) in comparison to healthy controls. An inverse significant correlation between SLEDAI-2K scores for disease activity and F/B ratio (r = −0.451; p = 0.04 ) was found. However, an inverse nonsignificant correlation between SLEDAI-2K scores for disease activity and Lactobacillus (r = −0.155; p = 0.51 ) was detected. Conclusion. Compared to healthy controls, recently diagnosed SLE Egyptian patients have an altered fecal microbiota profile with significant lowering of both F/B ratio and Lactobacillus abundance, which is weakly correlated with disease activity.

scholarly journals SAT0181 ALTERATIONS OF PERIPHERAL LYMPHOCYTE SUBSETS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND THEIR CHANGES AFTER OUR NEW IMMUNOREGULATORY COMBINATION THERAPIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1031.2-1032
Author(s):  
J. Q. Zhang ◽  
S. X. Zhang ◽  
L. Xue ◽  
J. Qiao ◽  
M. T. Qiu ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Lupus Erythematosus ◽  
Low Dose ◽  
Lymphocyte Subsets ◽  
Peripheral Lymphocyte ◽  
Combination Therapies ◽  
Systemic Lupus ◽  
T Subsets ◽  
The Absolute

Background:Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by abnormal activation of circulating lymphocytes and overproduction of autoantibodies1. Breakdown of self-tolerance is considered as a critical cause in the development of SLE2. However, the quantitative changes of lymphocyte subsets in SLE are unclear. Since low-dose IL-2 and several drugs have been used to promote the proliferation of regulatory T cells (Tregs)3, we developed immunoregulatory therapies using these drugs to rebalance effector T cells with Tregs and test whether they are benefit to remission disease activity of SLE.Objectives:To observe the different levels of peripheral lymphocyte subsets at the first laboratory examination of SLE patients with those of healthy controls (HCs) and to evaluate the effect of immunoregulatory combination therapies on levels of lymphocyte subsets in patients with SLE.Methods:From September 2014 to December 2019, a total of 985 diagnosed patients with SLE (878 females, 107 males, mean age 42.99±13.37 years) and 206 healthy adults were enrolled in this retrospective cross-sectional study. And 795 patients with SLE (711 females and 84 males, mean age 38.26±15.242 years) were received the immunomodulatory drugs (IMiDs) such as low-dose interleukin-2, rapamycin, metformin, retinoic acid, coenzymes Q10 or other immunomodulatory treatments. The absolute numbers of T, B, NK, CD4+T, CD8+T, Th1, Th2, Th17 and CD4+CD25+Foxp3+T regulatory cells (Tregs) in peripheral blood (PB) of these individuals were measured by Flow Cytometer (FCM) combined with standard absolute counting beads.Results:As compared with those of HCs, patients with SLE had lower absolute numbers of total T, NK, and CD4+T but higher proportions of all lymphocyte subpopulations except NK, CD4+T cells(P< 0.001) (Figure 1 A, C). Notably, the absolute numbers and proportions of Tregs as well as Th1 in CD4+T subsets were decreased (P<0.05) (Figure 1 B, D). Further, there was a significant increase in the ratio of Teffs/Tregs such as Th1/Tregs, Th2/Tregs and Th17/Tregs (P<0.05) (Figure 1 E). After receiving immunoregulatory combination therapies, the absolute numbers and proportions of T, NK, CD4+T, and CD8+T were increased, while the proportion of B cells was decreased (Figure 2 A, C); the absolute numbers of most CD4+T subsets as well as the proportions of only Th1 and Tregs were significantly increased (P< 0.001) (Figure 2 B, D). The ratios of Th1/Th2 and Th1/Tregs increased while that of Th17/Tregs and Th2/Tregs decreased (P<0.01) (Figure 2 E).Conclusion:Quantitative and functional alterations of peripheral lymphocyte subsets, especially reduced Tregs, play crucial roles in the pathogenesis of the patients. Immunoregulatory combination therapies mainly promote the proliferation and functional recovery of Tregs to rebalance pro- and anti-inflammatory T cells in patients with SLE for patients’ symptoms remission.References:[1]Sharabi A, Tsokos GC. T cell metabolism: new insights in systemic lupus erythematosus pathogenesis and therapy. Nat Rev Rheumatol 2020 doi: 10.1038/s41584-019-0356-x [published Online First: 2020/01/18][2]Durcan L, O’Dwyer T, Petri M. Management strategies and future directions for systemic lupus erythematosus in adults. Lancet 2019;393(10188):2332-43. doi: 10.1016/S0140-6736(19)30237-5 [published Online First: 2019/06/11][3]Spolski R, Li P, Leonard WJ. Biology and regulation of IL-2: from molecular mechanisms to human therapy. Nat Rev Immunol 2018;18(10):648-59. doi: 10.1038/s41577-018-0046-y [published Online First: 2018/08/10]Acknowledgments :None.Disclosure of Interests:None declared

Sign in / Sign up

Export Citation Format

Share Document