THU0325 REDUCED OF TREG CELLS ASSOCIATED WITH THE DISEASE ACTIVITY OF ANCA-ASSOCIATED VASCULITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 392-392
Author(s):  
R. Wu ◽  
R. Su ◽  
T. Ding ◽  
H. Xue ◽  
J. An ◽  
...  
Keyword(s):  
Disease Activity ◽  
Immune Tolerance ◽  
Th17 Cells ◽  
Absolute Number ◽  
Treg Cells ◽  
Healthy Controls ◽  
Activity Group ◽  
Anca Associated Vasculitis ◽  
T Subsets ◽  
The Absolute

Background:Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune disease that can cause systemic organ damage, characterized with the presence of abnormal antibodies (ANCAs) in the circulation and the small- and medium-vessel vasculitis[1].However,the etiology of AAV remained unclear. Several observations have showed that the breakdown of immune tolerance caused by many complex interactions was involved in the pathogenesis of AAV[2].It has been confirmed that the disorder of the CD4+T cell,especially the imbalance of Th17 and Treg cells can destroy the immune tolerance and cause many autoimmune disease[3]. But the relationship between the Th17/Treg and AAV is unknown.Objectives:We investigated the absolute numbers of CD4+T subsets cells in peripheral blood of patients with AAV and healthy adults,and then compared them in different disease activity of AAV to explore the role of CD4+T subsets cells in the pathogenesis and development of AAV.Methods:49 patients with AAV,hospitalized at the Second Hospital of Shanxi Medical University from the May 2016 to the November 2019 were enrolled, and 31 age and gender-matched healthy adults were anticipated as controls.According to BVAS, the patients were divided into disease-activity group (BVAS≥15, n=27) and non-disease-activity group (BVAS<15, n=22). The absolute numbers of CD4+T subsets cells including Th17 and Tregs in peripheral blood of these individuals were detected by flow cytometry.We analyzed whether there was difference of CD4+T subsets between the patients and healthy controls,and between disease-activity group and non-disease-activity group.Results:There was significant decreased level of Treg cells in the patients with AAV compared with healthy controls,especially in the disease-activity group. The absolute numbers of Treg cells was decreased in the patients with AAV compared with healthy controls (P<0.001) leading to a higher Th17/Treg ratio in the patients (P<0.01).Similarly,the absolute number of Treg cells was decreased in the disease- activity group (P<0.01) compared with the non-disease-activity group, and the absolute number of Treg cells was significant negative correlation with the disease activity indexes such as BVAS (r=-0.342,P=0.016), erythrocyte sedimentation rate(ESR) (r=-0.315,P=0.027) and C-reactive protein(CRP) (r=-0.305,P=0.033). But there was no statistically significant in the absolute number of Th17 cells between the patients and healthy controls, and between disease-activity group and non-disease-activity group.Conclusion:The results we investigated here suggested that the decreased number of Treg cells failed to control autoimmune inflammatory response and maintain immune tolerance, and the disease activity of AAV was associated with the reduced number of Treg cells.Figure 1.(A-C) Characteristics of the absolute number of Th17 cells and Treg cells in peripheral blood of healthy controls (n=31) and the patients with AAV (n=49). There was significant decreased level of Treg cells in the patients with AAV compared with healthy controls leading to a higher Th17/Treg ratio in the patients with AAV. (D-F) The absolute number of Treg cells was decreased in the disease- activity group (n=27) compared with the non-disease-activity group (n=21). The absolute number of Th17 cells and Treg cells was detected by flow cytometry. Statistical analyses were performed by the Mann-Whitney U test. *p<0.05,**p<0.01, ***p<0.001.References:[1]Cosmi, L., Th17 and Treg lymphocytes as cellular biomarkers of disease activity in Granulomatosis with Polyangiitis. Eur J Immunol, 2017.47(4): p. 633-636.[2]Pagnoux, C.,Updates in ANCA-associated vasculitis.Eur J Rheumatol, 2016.3: p. 122-133.[3]Diller, M.L., et al., Balancing Inflammation: The Link between Th17 and Regulatory T Cells. Mediators Inflamm, 2016.2016: p. 6309219.Disclosure of Interests:None declared

SAT0278 LOW-DOSE IL-2 RESTORES TREG-MEDIATED IMMUNE TOLERANCE IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1083-1084
Author(s):  
R. Wu ◽  
R. Su ◽  
T. Ding ◽  
H. Xue ◽  
J. An ◽  
...  
Keyword(s):  
Immune Tolerance ◽  
Low Dose ◽  
Granulomatosis With Polyangiitis ◽  
Absolute Number ◽  
Treg Cells ◽  
Healthy Controls ◽  
Short Term ◽  
Anca Associated Vasculitis ◽  
T Subsets ◽  
The Absolute

Background:Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune disease that can cause systemic organ damage, including granulomatosis with polyangiitis(GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis(EGPA)[1]. Several observations have showed that the breakdown of immune tolerance was involved in the pathogenesis of AAV [2], furthermore, a single, open and clinical trial demonstrates that IL-2 can be used to treat patients with GPA [3]. But there is still a lack of understanding of the relationship between Th17 / Treg and AAV and evidence for the therapeutic effect of IL-2 on AAV, which needs further exploration.Objectives:We first measured the absolute number of CD4+T subsets in peripheral blood of patients to explore the pathogenesis of AAV, and then investigated the effects of short-term and low-dose recombinant human IL-2 (rhIL-2) on CD4+T subsets of patients to analyze the regulatory effect of IL-2 on AAV.Methods:49 patients with AAV, hospitalized at the Second Hospital of Shanxi Medical University from the May 2016 to the November 2019 were enrolled, including 36 patients who were only received conventional glucocorticoids and DMARDs, and other 13 patients who were not only received these treatments but were also injected subcutaneously rhIL-2(50WIU/day for a 5-day course). 31 age and gender-matched healthy adults were selected as controls. The absolute number of Th17 and Treg cells in peripheral blood of health controls and the patients before and after treatment was detected by flow cytometry.Results:There was significant decreased level of Treg cells in the patients with AAV compared with healthy controls (P<0.001) leading to a higher Th17/Treg ratio in the patients with AAV, but there was no statistically significant in the absolute number of Th17 cells between the patients and healthy controls. After the treatment of short-term and low-dose IL-2, there was a significant increase in the absolute number of Treg cells (P<0.01) leading to a decrease in the ratio of Th17 and Treg (p<0.05).The absolute number of Th17 had a trend towards higher values but was not statistical significance.Conclusion:The difference of Treg cells between the patients and healthy controls suggested that the decreased number of Treg cells failed to control autoimmune inflammatory response contributing to the pathogenesis of AAV. After the treatment of short-term and low-dose rhIL-2, there was a more significant increase in the absolute number of Treg cells showing that IL-2 could selectively stimulate the growth of Treg cells and restore the Treg-mediated immune tolerance in patients with AAV to achieve disease remission.References:[1]Cosmi, L.,Th17 and Treg lymphocytes as cellular biomarkers of disease activity in Granulomatosis with Polyangiitis.Eur J Immunol, 2017.47(4): p. 633-636.[2]Pagnoux, C.,Updates in ANCA-associated vasculitis.Eur J Rheumatol, 2016.3: p. 122-133.[3]Rosenzwajg, M., et al.,Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial.Annals of the Rheumatic Diseases, 2019.78(2): p. 209-217.Disclosure of Interests:None declared

scholarly journals AB0490 CIRCULATING REGULATORY T CELLS WERE ABSOLUTELY DECREASED IN TAKAYASU’S ARTERITIS PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1542.1-1543
Author(s):  
W. Jia ◽  
J. Xie ◽  
X. Wang ◽  
C. Gao ◽  
G. Liu ◽  
...  
Keyword(s):  
Takayasu Arteritis ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Takayasu’S Arteritis ◽  
Absolute Number ◽  
Treg Cells ◽  
Healthy Controls ◽  
Takayasu's Arteritis ◽  
Tnf Α ◽  
The Absolute

Background:Takayasu arteritis (TA) refers to chronic progressive non-specific inflammation that involves the aorta and its main branches, causing stenosis and occlusion of arteries in different parts, and ischemic manifestations in the corresponding parts. A variety of immune dysfunctions are involved in the occurrence and development of TA(1)Recent studies have shown that Th17/Treg imbalance plays an important role in the pathogenesis of Takayasu’s arteritis, in which T help 17 cells (Th17) cells are up-regulated in TA patients(2). Th17 cells are closely related to Treg cells during differentiation. There are few studies on the expression level of CD4+CD25+FOX3+T lymphocyte (Treg) cells. This study aims to study the clinical significance of Treg cell expression in peripheral blood of patients with Takayasu’s arteritis.Objectives:To analyze the levels of circulating lymphocyte subsets and serum cytokines in patients with takayasu arteritis (TA), and explore the relationship between their changes and TA disease activity.Methods:A total of 46 TA patients and 43 gender-age-matched healthy controls were enrolled. According to the NIH standard, 30 patients were in active disease. Flow cytometry was used to detect the absolute numbers and ratios of Th1, Th2, Th17 and Treg cells in peripheral blood of all subjects. Magnetic bead-based multiplex immunoassay was used to detect cytokines and statistical analysis was performed.Results:Compared with the healthy controls, the absolute number and proportion of peripheral Treg cells of TA patients significantly decreased while those of Th17 cells increased significantly, leading to the increased ratio of Th17 / Treg. Compared with the inactive group, the TA active group had significantly increased IL-6 and TNF-α, and there was no significant difference in the expression of Th17 cells and Treg cells.Conclusion:In peripheral blood of TA patients, Treg cells decreased, while Th17 cells increased as compared with healthay controls, leading to an imbalance between Th17 and Treg cells. The levels of IL-6 and TNF-α were related to disease activity.References:[1]Russo, R.A.G. and M.M. Katsicas, Takayasu Arteritis. Front Pediatr, 2018. 6: p. 265.[2]Misra, D.P., S. Chaurasia, and R. Misra. Increased Circulating Th17 Cells, Serum IL-17A, and IL-23 in Takayasu Arteritis. Autoimmune Dis, 2016. 2016: p. 7841718.Figure 1.Characteristics of the absolute numbers and proportions of Th1cells,Th2cells,Th17 cells and CD4Treg cells in the PB of patients with TA.(A-C)The levels of Th17 cells and the ratio of Th1/Treg,Th2/Treg,Th17/Treg in PB were significantly increased in patients with TA (n=46). The absolute number and the proportion of CD4Treg cells were significantly decreased in TA(n=46). (D-F) The absolute number of Th2 cells and ratio of Th2/Treg in PB were significantly decreased in active patients with TA (n=30).Neither the absolute number nor proporation of Th1, Th17 and Treg cells was altered significantly between active TA patients(n=30) and inactive TA patients(n=16).*P<0.05; **P<0.001. P<0.05 was considered statistically significant.TA,takayasu arteritis;PB peripheral blood;Tregs, regulatory Tcells.Figure 2.Characteristics of serum concentrations of cytokine (including IL-6, IL-10, IL-17 and TNF-α) between active TA patients(n=30) and inactive TA patients(n=16).(A,D)In terms of cytokines, the concentration of IL-6 and TNF-α was significantly up-regulated,(B,C)but no significant changes in IL-10, and IL-17 were found.*P<0.05; **P<0.001. P < 0.05 was considered statistically significant.Disclosure of Interests:None declared

scholarly journals Decreased Absolute Number of Circulating Regulatory T Cells in Patients With Takayasu’s Arteritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Wen Jia ◽  
Zi-Li Fu ◽  
Xia Wang ◽  
Jing Luo ◽  
Cheng-Lan Yan ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Disease Activity ◽  
Th17 Cells ◽  
Absolute Number ◽  
Treg Cells ◽  
Th2 Cells ◽  
Negatively Associated ◽  
Tnf Α ◽  
The Absolute

BackgroundTakayasu’s arteritis (TA) is a type of primary large vessel vasculitis. Th1, Th17, and Tfh cells have been reported to be associated with TA relapse. However, the relationship between regulatory T cells (Tregs) and TA remains unclear.ObjectiveTo analyze the levels of circulating lymphocytes, especially Treg cells (CD4+CD25+FOXP3+ T cells) and serum cytokines in TA patients and explore their relationship with their changes and TA disease activity.MethodsA total of 57 TA patients and 43 sex- and age-matched healthy controls (HCs) were enrolled. According to NIH standards, 36 patients had active disease status. Flow cytometry combined with counting was used to detect the absolute numbers and ratios of Th1, Th2, Th17, and Treg cells in the peripheral blood of all the subjects. Magnetic bead-based multiplex immunoassay was used to detect cytokines.ResultsCompared to HCs, the absolute number and proportion of peripheral Treg cells in TA patients was significantly decreased, while Th17 cells were significantly increased. Furthermore, compared to the inactive group, the TA active group had significantly increased levels of interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α, but lower IL-10 levels. The absolute number of Th2 cells was negatively associated with platelet (PLT) and NIS scores in TA patients. The proportion of Th2 cells was negatively associated with the erythrocyte sedimentation rate in TA patients. After treatment, Treg cells were markedly increased.ConclusionThere was a Th17-Treg cell imbalance with a significant reduction in peripheral Treg cells and an increase in Th17 cells in TA patients compared to the HCs. The levels of IL-6, IL-10, IL-17, and TNF-α appeared to be related to disease activity.

scholarly journals POS0396 THE LEVEL OF PERIPHERAL REGULATORY T CELLS IS ASSOCIATED WITH THE CHANGES OF INTESTINAL MICROBIOTA IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 427-428
Author(s):  
R. Wu ◽  
J. An ◽  
T. Ding ◽  
H. Xue ◽  
X. F. Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Intestinal Microbiota ◽  
Immune Tolerance ◽  
Cd4 T Cells ◽  
Absolute Number ◽  
Treg Cells ◽  
Genus Level ◽  
T Subsets ◽  
The Absolute

Background:Rheumatoid arthritis (RA) is a systemic autoimmunity inflammation disease characterized with chronic aggressive arthritis and the presence of abnormal antibodies. Several observations showed that the breakdown of immune tolerance caused by many complex interactions was involved in the development of RA[1]. However, the pathogenesis of RA remained unclear. It has been confirmed that the imbalance of Th17 and Treg cells play a crucial role in destroying immune tolerance [2]. Besides, researches showed that intestinal microbiota can influence host immunity by acting on the immune cells to play pro-inflammatory or anti-inflammatory effect, and in turn immune system can also regulate the microbiota[3, 4]. Thus, a frontier point of view in the field of rheumatism, immune microecology, was proposed, which is a novel concept for the breakdown of immune tolerance. Studies have confirmed that there was an imbalance of intestinal microbiota in patients with RA [4]. But the relationship between the CD4+T subsets cells and intestinal microbiota in RA is unknown.Objectives:We detected and compared the absolute number of CD4+T cells subsets in the peripheral blood and the proportion or abundance of intestinal microbiota in patients with RA and healthy adults, and then analyzed the relationship between them to explore the role of CD4+T cells subsets and intestinal microbiota in the pathogenesis of RA.Methods:We collected the sample of stool and blood from 15 patients with RA hospitalized at the Second Hospital of Shanxi Medical University and 8 age and gender-matched healthy controls(HC). The absolute number of CD4+T cells subsets including Th1, Th2, Th17 and Treg cells were detected by flow cytometry. The 16S rRNA in the stool specimens were sequenced by the Roche/45 high-throughput sequencing platform. We analyzed whether there was correlarion between CD4+T subsets cells and intestinal microbiota.Results:Patients with RA had a higher level of Christensenellaceae and a lower level of Pseudomonadaceae as compared with those of HCs at the family level (p<0.05). And at the genus level, the patients with RA had higher levels of Ruminococcus torques, Christensenellaceae R-7, Ruminiclostridium 9 and Ruminococcus 1 compared with those of HCs (p<0.05) (Figure 1).And the Ruminococcus torques at the genus level was negative correlated with the absolute number of Treg cells (p<0.001) (Figure 2).Conclusion:The results here suggested that there were different proportion or abundance of intestinal microbiota between the patients with RA andHCs. And the changes of intestinal microbiota such as Ruminococcus torques were associated with Treg cells, further indicating that the imbalance of intestinal microbiota in RA can destory the immune tolerance. The above results uncovered that the intestinal microbiota had immunomodulatory function, which may be the upstream mechanism participated in the pathogenesis of RA.References:[1]Weyand CM, Goronzy JJ. The immunology of rheumatoid arthritis. Nat Immunol 2021, 22(1): 10-18.[2]Weyand CM, Goronzy JJ. Immunometabolism in the development of rheumatoid arthritis. Immunol Rev 2020, 294(1): 177-187.[3]Brown EM, Kenny DJ, Xavier RJ. Gut Microbiota Regulation of T Cells During Inflammation and Autoimmunity. Annu Rev Immunol 2019, 37: 599-624.[4]du Teil Espina M, Gabarrini G, Harmsen HJM, Westra J, van Winkelhoff AJ, van Dijl JM. Talk to your gut: the oral-gut microbiome axis and its immunomodulatory role in the etiology of rheumatoid arthritis. FEMS Microbiol Rev 2019, 43(1).Figure 1.At the family level (a-b) and the genus level(c-f), the relative abundance of intestinal microbiota in patients with RA and HCs were different. Data were expressed as median (Q1, Q3) and analyzed by Wilcoxon test. (*** P < 0.001, **P < 0.01 and *P < 0.05).Figure 2.A heatmap shows the correlation between the intestinal microbiota and CD4+T cells in patients with RA, and Ruminococcus torques at the genus level was negative related with Treg cells. (Colors indicate the Spearman rank correlation, *** P < 0.001).Disclosure of Interests:None declared

scholarly journals Blockade of NF-κB Translocation and of RANKL/RANK Interaction Decreases the Frequency of Th2 and Th17 Cells Capable of IL-4 and IL-17 Production, Respectively, in a Mouse Model of Allergic Asthma

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3117
Author(s):  
Izabela Gregorczyk ◽  
Agnieszka Jasiecka-Mikołajczyk ◽  
Tomasz Maślanka
Keyword(s):  
T Cells ◽  
Allergic Asthma ◽  
Cd4 T Cells ◽  
Th17 Cells ◽  
Nuclear Factor Κb ◽  
Absolute Number ◽  
Treg Cells ◽  
Therapeutic Strategies ◽  
Receptor Activator ◽  
The Absolute

The main purpose of this study was to investigate whether the blockade of the interaction between the receptor activator of nuclear factor-κB (NF-ĸB) ligand (RANKL) and its receptor RANK as well as the blockade of NF-κB inhibitor kinase (IKK) and of NF-κB translocation have the potential to suppress the pathogenesis of allergic asthma by inhibition and/or enhancement of the production by CD4+ and CD8+ T cells of important cytokines promoting (i.e., IL-4 and IL-17) and/or inhibiting (i.e., IL-10 and TGF-β), respectively, the development of allergic asthma. Studies using ovalbumin(OVA)-immunized mice have demonstrated that all the tested therapeutic strategies prevented the OVA-induced increase in the absolute number of IL-4- and IL-17-producing CD4+ T cells (i.e., Th2 and Th17 cells, respectively) indirectly, i.e., through the inhibition of the clonal expansion of these cells in the mediastinal lymph nodes. Additionally, the blockade of NF-κB translocation and RANKL/RANK interaction, but not IKK, prevented the OVA-induced increase in the percentage of IL-4-, IL-10- and IL-17-producing CD4+ T cells. These latter results strongly suggest that both therapeutic strategies can directly decrease IL-4 and IL-17 production by Th2 and Th17 cells, respectively. This action may constitute an important mechanism underlying the anti-asthmatic effect induced by the blockade of NF-κB translocation and of RANKL/RANK interaction. Thus, in this context, both these therapeutic strategies seem to have an advantage over the blockade of IKK. None of the tested therapeutic strategies increased both the absolute number and frequency of IL-10- and TGF-β-producing Treg cells, and hence they lacked the potential to inhibit the development of the disease via this mechanism.

scholarly journals FRI0261 DIFFERENTIAL EXPRESSION OF PERIPHERAL CD4+ T CELLS IN PATIENTS WITH SYSTEMIC SCLEROSIS AND MIXED CONNECTIVE TISSUE DISEASE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 714.1-715
Author(s):  
L. Shang ◽  
T. Zhang ◽  
J. Luo ◽  
J. Yuan ◽  
C. Gao ◽  
...  
Keyword(s):  
T Cell ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Lymphocyte Subsets ◽  
Pulmonary Involvement ◽  
Absolute Number ◽  
Treg Cells ◽  
Th2 Cells ◽  
Th1 Cells ◽  
The Absolute

Background:The CD4+T cell subsets plays an important role in its pathogenesis, and its new research are constantly being published, but its specific changes between SSc and MCTD are still unclear.Objectives:The aim of the present study was to explore the absolute numbers of CD4+T subsets in peripheral blood(PB) of patients with SSc and MCTD using our modified flow cryometric method and investigate the role in the pathogenesis of both.Methods:The PB samples from 54 patients with SSc, 51 patients with MCTD as well as 30 healthy control subjects were analyzed for lymphocyte subsets using flow cytometry. Of these patients, 19 had pulmonary involvement, including 9 patients with SSc and 10 patients with MCTD. Using directly the percentages from flow cytometry combined with internal standard beads calculated absolute number of peripheral lymphocyte subsets from the subjects in each group.Results:Although there were some changes among CD4+T cell subsets in PB from these SSc patients and MCTD patients, the major alteration was the reductions of Treg cells. Compared with the normal controls, the absolute number of CD4+CD25+FOXP3+Treg cells were significantly decreased in SSc patients and MCTD patients, and the absolute number of Th1 cells in MCTD patients is also significantly reduced. Notably, the absolute numbers of Th17 and Th2 cells were not different from those of normal controls, but the ratios of Th17/Treg in SSc patients and MCTD patients were significantly higher, causing by insufficient number of Treg cells (Fig 1). In addition, in patients with pulmonary involvement, we found that the absolute number of Treg cells was significantly reduced in patients with MCTD, while the absolute number of Th2 cells and Th17 cells was significantly reduced in patients with SSc(Fig 2).Fig 1.Comparison of the levels of CD4+T lymphocyte subsets in SSc patients, MCTD patients and healthy controls: (A) The absolute number of peripheral Th1 cells in patients with MCTD was significantly reduced; (B and C) There was no significant difference in the absolute number of Th2 cells in peripheral blood of different subjects; (D and E) The ratio of Th17/Treg cells in PB of patients with SSc and MCTD were significantly higher.*P< 0.05; **P< 0.01; ***P< 0.001.Conclusion:The number of peripheral Treg cells in patients with SSc and MCTD was significantly reduced, suggesting that that SSc and MCTD progression is associated with the imbalances between pro-inflammation cells to anti-inflammation Treg cells. In addition, we also found that the decrease in peripheral numbers of Treg cells may contribute to the development of MCTD-associated lung disease, whereas in SSc patients who had lung involvement, the reduce in peripheral number of Th17 cells may result in a severe imbalance of Th17/Treg cells, thereby promoting disease progression.Fig 2.Comparison of the levels of CD4+T lymphocyte subsets in patients who had pulmonary involvement and healthy controls: (A) There was no significant difference in the absolute number of Th1 cells in peripheral blood of different subjects; (B and C) The absolute number of peripheral Th2 cells and Th17 cells in patients with SSc were significantly reduced; (D and E) The ratio of Th17/Treg cells in PB of patients with MCTD were higher.*P< 0.05; **P< 0.01; ***P< 0.001.References:[1]Liu M, Wu W, Sun X, et al. New insights into CD4(+) T cell abnormalities in systemic sclerosis. Cytokine Growth Factor Rev. 2016 Apr; 28:31-6. doi: 10.1016/j.cytogfr.2015.12.002.Acknowledgments:NoneDisclosure of Interests:None declared

scholarly journals Elevated Peripheral T Helper Cells Are Associated With Atrial Fibrillation in Patients With Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xin Wang ◽  
Hongxuan Fan ◽  
Yongle Wang ◽  
Xufang Yin ◽  
Guangying Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Atrial Fibrillation ◽  
Propensity Score ◽  
Th17 Cells ◽  
Demographic Data ◽  
Absolute Number ◽  
Treg Cells ◽  
Th1 Cells ◽  
T Helper ◽  
The Absolute

Patients with rheumatoid arthritis (RA) have a significantly high risk of atrial fibrillation (AF). This study aimed to compare the absolute and relative changes in peripheral T cells in patients with RA who were also affected with and without AF. To help make an early diagnosis and prevent the initiation and progression of AF, the changes in the lymphocyte subsets were assessed in RA patients with and without AF. A propensity score matching (PSM) system (1:3) was used to perform a matched case-control study with 40 RA-AF cases and 120 RA controls. Changes in the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-citrullinated peptide antibody (ACPA), and rheumatoid factor (RF) were examined. The percentage and absolute number of T, B, natural killer (NK), T helper (Th)1, Th2, Th17, and T-regulatory (Treg) cells in the peripheral blood of patients with and without RA-AF were determined using flow cytometry. Univariate and multivariate analyses were performed to determine the association between peripheral lymphocytes and RA-AF. Demographic data, ESR, CRP, ACPA, and the percentage, as well as the absolute value of B, NK, Th2, and Treg cells, showed no significant differences between the propensity score-matched groups of RA and RA-AF. Meanwhile, the absolute number and percentage of Th1 cells, the absolute number of Th17 cells, the ratio of Th1/Treg, Th17/Treg, and RF were significantly higher in patients with RA-AF than those in the control groups (P &lt; 0.05). Univariate and multivariate logistic regression analyses also revealed that the percentage of Th1 cells, the absolute number of Th17 cells, and the ratio of Th1/Treg were associated with a significantly higher risk of AF. This PSM study demonstrated that the incidence of AF was higher in RA patients with Th cell immunological derangements.

scholarly journals AB0630 IMBALANCE BETWEEN Th17 AND REGULATORY T CELLS IN PATIENTS WITH PM/DM COMBINED WITH EBV/CMV VIRAEMIA

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1610.1-1611
Author(s):  
X. Zheng ◽  
R. Su ◽  
Y. Liu ◽  
X. Li ◽  
C. Wang
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Th17 Cells ◽  
Absolute Number ◽  
Treg Cells ◽  
Th2 Cells ◽  
Cmv Infection ◽  
Infection Group ◽  
The Absolute

Background:Dermatomyositis and polymyositis (DM/PM) are associated with muscle weakness and inflammatory infiltration within the skeletal muscle. The numerical and functional defects of immune cells, due to long-term uses of glucocorticoids and disease-modifying anti-rheumatic drugs (DMARDs) together with immune disturbances associated with disease itself, lead to high risks in opportunistic infections, such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV).1-2We want to observe changes of peripheral lymphcytessubsets in PM/DM patients with EBV and/or CMV infection,especially whether there is imblance between Th17 and Treg cells.Objectives:To investigate the characteristics of peripheral lymphocyte subsets in PM/DM with EBV and/or CMV infection, especially the Th17 and Treg cells.Methods:From February 2016 to November 2019, PM/DM patients with EBV and/or CMV viremia (infection group, n=34) and without infection (non-infection group, n=31) as well as healthy adult controls (n=20) were enrolled in our study. Absolute numbers of total T, total B, NK, CD4 + T, CD8 + T cells, and CD4 + T subsets (Th1, Th2, Th17 and Treg cells) in peripheral blood by flow cytometry combined with standard absolute counting beads.Results:(1) Compared with PM/DM patients without infection, 34 PM/DM patients with EBV and/or CMV infection, including 12 patients with EBV, 20 patients with CMV, 2 patients combined EBV and CMV, the absolute number of total T lymph cells (P=0.019), total B lymph cells (P=0.037), NK cells (P=0.033), CD4 + T cells (P=0.000), Th1 cells (P=0.014), Th2 cells (P=0.003), Th17 cells (P=0.003), Treg cells (P=0.004) lower than its of (P=0.003) patients without infection, the absolute number of CD8 + T cells (P=0.427) has no obvious difference between them.(2) And its the absolute number of total T lymph cells (P=0.000), total B lymph cells (P=0.003), NK cells (P=0.000), CD4 + T cells (P=0.000), CD8 + T cells (P=0.006), Th1 cells (P=0.000), Th2 cells (P=0.001), Th17 cells (P=0.000) and Treg cells (P=0.000) significantly lower than healthy control.(3) Compared with the healthy control,the absolute number of total T lymph cells (P=0.000), NK cells (P=0.000), CD4 + T cells (P=0.031), CD8 + T cells (P=0.000), Th1 cells (P=0.002), Th2 cells (P=0.031), and Treg cells (P=0.000) in PM/DM without infection evidently lower, but there is no siginificant difference in absolute number of total B lymph cells (P=0.19) and Th17 cells (P=0.171).Conclusion:We show that the absolute number of peripheral blood lymphocytes and CD4+T subsets in patients with PM/DM with EBV and/or CMV viremia is further reduced. In addition to Treg cells, a decrease in Th17 cells may also be an important feature of EBV and/or CMV infection in DM/PM. These cell reductions may be the cause and risk indicator of viral infections.References:[1]Yang X, Hao Y, Zhang X, et al. Mortality of Chinese patients with polymyositis and dermatomyositis. Clin Rheumatol. 2020 Jan 4. doi: 10.1007/s10067-019-04910-w. [Epub ahead of print]. PMID: 31902027[2]Matsushita T,Kobayashi T, Kano M, et al. Elevated serum B-cell activating factor levels in patients with dermatomyositis: Association with interstitial lung disease. J Dermatol.2019:46:1190-6. doi:10.1111/1346-8138.15117Figure.Absolute numbers of peripheral lymphocyte subsets between healthy controls and patients were assessed by fow cytometry using oneplatform method. PM/DM infection group (n=34), PM/DM non- infection group(n=31)and healthy control group (n = 20).(*p<0.05, **p<0.01, ***p<0.001)Disclosure of Interests:None declared

scholarly journals POS1006 ABERRANT Th17 CELLS EXPANSION AND RISK FACTORS IN ANKYLOSING SPONDYLITIS PATIENTS COMPLICATED WITH CARDIOVASCULAR EVENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 771.2-771
Author(s):  
T. Ding ◽  
B. C. LI ◽  
R. Su ◽  
X. F. LI ◽  
C. Wang
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Ankylosing Spondylitis ◽  
Odds Ratio ◽  
Cardiovascular Events ◽  
Th17 Cells ◽  
Absolute Number ◽  
Treg Cells ◽  
Th1 Cells ◽  
The Absolute

Background:The incidence of Ankylosing Spondylitis (AS) complicated with cardiovascular diseases (CVD) has increased in recent years [1]. However, identification of risk factors indicating the development of CAD in AS patients is lacking. Th17 cells are increasingly recognized to be important in atherogenesis [2]. However, the role of these cells in the pathogenesis of ankylosing spondylitis patients complicated with cardiovascular events remains elusive.Objectives:This study aimed to assess the level of circulating Th17 cells as well as other lymphocyte subsets such as Treg, Th, Ts, and NK cells in AS combined with CVD, and further to evaluate whether elevations in special PBMC subpopulations in AS patients indicate an increased risk of CVD.Methods:Samples were assessed from 141 AS patients hospitalized at the Second Hospital of Shanxi Medical University (60 AS patients combined with CVD and 81 AS patients without CVD) and 100 healthy controls. The absolute numbers of lymphocytes and CD4+ T cells in peripheral blood were determined using Flow Cytometer. The association between PBMC subpopulations and CVD development in AS patients were analyzed using multivariable logistic regression.Results:1. Compared with AS group, AS with CVD group exhibited significant increases in the number of Th17 cells (P=0.001) and Treg cells (P=0.046). The ratio of Th17/Treg was also increased (P=0.085).2. Analogous increases in the absolute number (P<0.001) and frequency (P<0.001) of Th1 cells, as well as the ratio of Th1/Th2 (P<0.001) and Th1/Treg (P=0.004) were also present in AS with CVD patients, compared to those without CVD.3. Compared to HCs, 141 AS patients showed significantly decreased Treg cells (P<0.012) and increased Th17/Treg (P=0.001).4. Logistic regression showed age (odds ratio: 1.09; 95% CI: 1.035-1.137), hypertension (odds ratio: 3.31; 95% CI: 1.152-9.528), diabetes (odds ratio: 8.03; 95% CI: 1.251-51.503), and elevated level of Th1 number (odds ratio: 1.01; 95% CI: 1.003-1.016) and DD (D-dimer) (odds ratio: 1.00; 95% CI: 1.000-1.002) were significantly correlated with the onset of CVD in AS patients.5. Smoke, increased Th17 level, and use of NSAIDS were also positively correlated with the onset of CVD although the P-values did not reach significant.Conclusion:Our data indicates aberrant expansion of Th17 cells in AS with CVD patients. Moreover, age, hypertension, diabetes, and increased level of Th1 in PBMC and DD are single independent risk factors for the presence of CVD in AS. The mechanisms of atherogenesis in AS may associate with the elevations in Th1 and Th17 cells. Imbalance of Th1/Th2 and Th17/Treg may be shared etiologic pathways of AS and CVD, providing attractive targets for the prevention and therapy of CVD development in AS patients.References:[1]Kim JH, Choi IA. Cardiovascular morbidity and mortality in patients with spondyloarthritis: A meta-analysis. Int J Rheum Dis (2020). doi: 10.1111/1756-185x.13970.[2]Saigusa R, Winkels H, Ley K. T cell subsets and functions in atherosclerosis. Nat Rev Cardiol. 2020 Jul;17(7):387-401. doi: 10.1038/s41569-020-0352-5.Figure 1.Compared with AS group, AS with CVD group exhibited significant increases in the number of Th17 cells (P=0.001) and Treg cells (P=0.046). The ratio of Th17/Treg was also increased (P=0.085). The absolute number (P<0.001) and frequency (P<0.001) of Th1 cells, as well as the ratio of Th1/Th2 (P<0.001) and Th1/Treg (P=0.004) were also present in AS with CVD patients.Disclosure of Interests:None declared.

scholarly journals AB0588 INFECTION AGGRAVATED DECREASE OF THE LEVEL OF TH17 AND TREG CELLS AND LOW-DOSE IL-2 REBALANCED TH17/TREG IN THE PERIPHERAL BLOOD OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1591.3-1591
Author(s):  
Y. Liang ◽  
H. Y. Wen ◽  
Y. Duan ◽  
Y. Liu ◽  
Z. Yu ◽  
...  
Keyword(s):  
T Cells ◽  
Low Dose ◽  
Lymphocyte Subsets ◽  
Absolute Number ◽  
Treg Cells ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Infection Group ◽  
The Absolute ◽  
Organ Infection

Background:Idiopathic inflammatory myopathies (IIM) are featured by a series of clinical presentation such as proximal muscle weakness, increased serum levels of creatine kinase and other muscle enzymes and involvement of other organs and systems[1, 2], which results in high morbidity and early mortality[3]. We have known the changes of the level of Th17 and Treg cells in IIM in previous studies[4-6]. However, whether infection affects lymphocyte subsets or not and whether the effect of low-dose interleukin-2 (IL-2) can be influenced by the use of immunosuppressants or not are still unclear.Objectives:The study aimed to explore the changes of lymphocyte subsets in patients of IIM with or without important organ infection, and the restoration of Th17/Treg after receiving low-dose IL-2.Methods:A total of 118 IIM patients were enrolled and classified into infection group and non-infection group based on the important organ infection. Of them, 48 cases were treated with low dose IL-2 (5.0*105IU for 5 days). The absolute number of peripheral total T, B, CD4+T, CD8+T, NK, Th1, Th2, Th17 and Treg cell subsets were analyzed by flow cytometry combined with absolute counting beads. Clinical data, laboratory examinations and the levels of peripheral lymphocyte subsets were analyzed retrospectively.Results:In these patients, especially in the infection group, the absolute number of T, CD4+T, CD8+T, NK, Th1, Th2, Th17 and Treg cells were significantly decreased as compared with that in the healthy controls, which were significantly increased by low dose IL-2 (especially Treg cells) treatment. The levels of ESR, LDH and HBDH and the ratio of Th17/Treg were significantly lower than those before IL-2 treatment (Z=-2.237, -2.083, -2.140, -3.663,P=0.025, 0.037, 0.032, 0.000). The 48 cases who received IL-2 treatment were divided into 2 groups according to whether they used immunosuppressants. There was no significant difference in the absolute number of T, B, CD4+T, CD8+T, Th1, Th2, Th17 and Treg cells, the proportion of Th17 and Treg cells and the ratio of Th17/Treg between the 2 groups (P>0.05).Conclusion:Global decrease in lymphocyte subsets was found in IIM patients, especially those who had important organ infection. A significant re-balance of Th17/Treg was observed after receiving treatment with low-dose IL-2. Furthermore, the restoration of lymphocyte subsets showed similar degree after treatment with or without immunosuppressants. Low-dose IL-2 may become a potential therapy for IIM patients. The mechanism of lymphocyte decrease in IIM is required further to study.References:[1]Clark K E N, Isenberg D A. A review of inflammatory idiopathic myopathy focusing on polymyositis[J]. European Journal of Neurology, 2017.[2]Tieu J, Lundberg IE, Limaye V. Idiopathic inflammatory myositis. Best Pract Res Clin Rheumatol. 2016. 30(1): 149-68.[3]Mandel DE, Malemud CJ, Askari AD. Idiopathic Inflammatory Myopathies: A Review of the Classification and Impact of Pathogenesis. Int J Mol Sci. 2017. 18(5).[4]Zhang SX, Wang J, Sun HH, et al. Circulating regulatory T cells were absolutely decreased in dermatomyositis/polymyositis patients and restored by low-dose IL-2. Ann Rheum Dis. 2019 .[5]Espinosa-Ortega F, Gómez-Martin D, Santana-De Anda K, Romo-Tena J, Villaseñor-Ovies P, Alcocer-Varela J. Quantitative T cell subsets profile in peripheral blood from patients with idiopathic inflammatory myopathies: tilting the balance towards proinflammatory and pro-apoptotic subsets. Clin Exp Immunol. 2015. 179(3): 520-8.[6]Feng M, Guo H, Zhang C, et al. Absolute reduction of regulatory T cells and regulatory effect of short-term and low-dose IL-2 in polymyositis or dermatomyositis. Int Immunopharmacol. 2019. 77: 105912.Acknowledgments:Thanks for the support of my teachers, classmates and my family.Disclosure of Interests:None declared

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