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 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 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

Th1 and Th17 Predominance in the Enthesitis-related Arthritis Form of Juvenile Idiopathic Arthritis

2009 ◽  
Vol 36 (8) ◽  
pp. 1730-1736 ◽  
Author(s):  
ANKIT MAHENDRA ◽  
RAMNATH MISRA ◽  
AMITA AGGARWAL
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Synovial Fluid ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Transforming Growth Factor ◽  
Health Assessment ◽  
Treg Cells ◽  
Th2 Cells ◽  
Median Frequency ◽  
Enthesitis Related Arthritis

Objective.A Th1 biased immune response in synovial fluid has been reported in children with polyarticular and extended oligoarticular-type juvenile idiopathic arthritis (JIA). We investigated T cell phenotypes including Th1, Th2, Th17, and Treg with emphasis on Th17 and Treg, in order to differentiate cytokines in the enthesitis-related arthritis (ERA) form of JIA.Methods.The frequencies of Th1, Th2, Th17, and Treg cells were determined by flow cytometry in peripheral blood (PB) and synovial fluid from patients with ERA and healthy subjects. Levels of interleukin 1ß (IL-1ß), IL-6, IL-21, IL-23, and transforming growth factor ß (TGF-ß), cytokines that influence Th17 lineage cells, were measured in paired plasma and synovial fluid (SF) samples by ELISA. Frequencies are expressed as percentages and cytokine levels as pg/ml.Results.There were no differences in blood samples in the frequency of Th1, Th2, Th17, and Treg cells between patients and controls. In paired samples, the median frequency of CD4+IFN-γ+ (20.49 vs 4.03; p < 0.005) and CD4+IL-17+ (2.27 vs 0.57; p < 0.01) cells was significantly higher in SF compared to PB, respectively; whereas the frequency of CD4+IL-4+ (1.79 vs 2.29; p < 0.04) cells was significantly reduced in the SF compared to PB. There was no difference in the frequency of regulatory T cells. Patients receiving methotrexate had fewer Th2 cells, whereas the Childhood Health Assessment Questionnaire score had a negative association with the frequency of Treg. Median levels of IL-1ß (p < 0.008), IL-6 (p < 0.0001), and IL-17 (p < 0.0001) were higher in SF than in plasma and levels of TGF-ß were lower (p < 0.001). Levels of IL-21 were similar in SF and plasma, whereas IL-23 was undetectable.Conclusion.In patients with ERA, peripheral blood Th1, Th2, Th17, and Treg cells were unchanged, but Th1 and Th17 cells were increased and Th2 cells were reduced in the SF compared to blood. Elevated IL-1ß and IL-6 in SF may be responsible for increased Th17 cells.

Functional Characterization of CD4+ T-Cells in Aplastic Anemia (AA)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1340-1340 ◽  
Author(s):  
Shahram Y Kordasti ◽  
Judith C. W. Marsh ◽  
Sufyan Al-Khan ◽  
Jie Jiang ◽  
Alexander E Smith ◽  
...  
Keyword(s):  
T Cells ◽  
Treatment Group ◽  
High Throughput ◽  
Cd4 T Cells ◽  
Th17 Cells ◽  
Absolute Number ◽  
Th2 Cells ◽  
Th1 Cells ◽  
Ifn Γ ◽  
Pre Treatment

Abstract Abstract 1340 We have examined the role of CD4+ T-cells in the pathogenesis of AA in 63 patients, 48 of whom were analyzed at diagnosis and 15 following immunosuppressive therapy (IST). Absolute numbers of CD4+ regulatory T cells (Tregs, defined as CD3+CD4+CD25highCD27+Foxp3+) were lower in pre-treatment AA patients compared to 10 healthy donors (HDs) (5.5 × 106 v 1.4 × 107)(p=0.01). In patients with severe (SAA) and very severe AA (VSAA), the absolute number and frequency of Tregs were lower than non-severe AA (NSAA) (4.4 × 106/L v 1 × 107/L)(p=0.01) and HDs (4.4 × 106/L v 3 × 107/L) (p<0.001). Absolute numbers of Th1 and Th2 cells in all pre-treatment patients were higher compared to HDs (6.4 × 107/L v 1.8 × 107/L)(p=0.03) for Th1 and (2.6 × 107/L v 2.4 × 106/L)(p=0.006) Th2 cells. Although mean percentages of AA Th17 cells were higher than in HDs (1.5% v 0.15%)(p=0.04), differences in absolute numbers were not significant. Absolute numbers of Th2 and Th17 cells were increased in SAA (1.3 × 107/L v 7.4 × 106/L for Th2)(p=0.01) compared to NSAA (5.7 × 106/L v 2.15 × 106/L for Th17)(p=0.02). Ratios of Th1/Tregs (p=0.003), Th2/Tregs (p=0.02), and Th17/Tregs (p=0.001) were higher in SAA and VSAA compared to NSAA. Percentage of both activated (CD4+CD45RA−CD25highFoxp3high) and resting (CD4+CD45RA+ CD25highFoxp3low) Tregs was decreased in AA patients, compared to HDs (p=0.004 and p=0.01), whereas cytokine secreting Tregs (CD4+CD45RA−CD25high Foxp3low) were increased in AA (p<0.003). Sorted Tregs from AA patients did not suppress cytokine secretion by autologous or HD T effectors (Te) cells in 1:1 co-cultures, whereas IL-2 and IFN-γ secretion by AA Te (CD4+CD25lowCD127high) was suppressible by allogeneic Tregs from HDs, confirming Tregs dysfunction. AA Tregs did not inhibit either CD154 or CD69 expression on Te cells. Tregs from AA patients secreted significantly more IFN-γ, TNF-α and IL-17 (p=0.02, p=0.02 and p=0.01, respectively) after 4 hours stimulation with PMA/Ionomycine compared to HDs. Expression levels of FoxP3, ROR□c and T-bet in AA Tregs was normal. IFN-γ secreting cells (Th1) were enriched using enrichment kit then further enriched by FACS sorting. CDR3 region products of TCR Vβ-chain were amplified using Vβ specific forward and Cβ reverse primers. CDR3 PCR products from AA patients and HDs were subjected 454 sequencing (Roche GS FLX titanium). Sequencing was performed to yield an average ‘depth’ in excess of 1000 clonally reads (1000x) for each sample specific CDR3 PCR amp icon. Reads were processed using Roche Amp icon Variant Analyzer software (AVA). Diversity of TCR receptors (measured by spectratyping and confirmed by high throughput deep sequencing) in AA Th1 cells was lower than HDs (p=0.037), as shown by the percentage and number of consensus clusters in total sequence reads. Interestingly, percentages of the most dominant CDR3 clones, revealed by high throughput sequencing, were higher in AA compared to HDs, regardless of spectratyping pattern. Global gene expression of Tregs was compared in 3 pre-IST AA patients and 5 HDs. A unique gene signature consisting of 86 genes that were significant was identified. There were 8 down regulated genes (fold change) in the pre-treatment group; PIN4 (−4.1), OR2T12 (−3.3), AMAC1 (−2.73), PERP (−2.69), UTS2 (−2.27), RNF139 (−2.13), COMMD9 (−2.09) and LOC100128356 (−2.01). The top 10 of 78 up-regulated genes in the pre-treatment group were HBB (19.5), PSME2 (13.8), CSDA (13.07), FAM127A (7.78), EXOSC1 (7.73), BPGM (7.43), CYSLTR1 (7.17), CHPT1 (6.96) and PLAC8 (6.71). qPCR analysis for CSDA, HBB, PSMiE2, PERP, PIN4, and UTS2 confirmed a similar trend to the microarray results. Interestingly absolute number of Tregs, and Th2/Treg ratio were higher in 10 IST responsive patients compared to 5 non-responsive patients (p=0.005 and 0.02, respectively). We show that expansion of Th1, Th2, Th17, and decreased/skewed Tregs immunophenotype and function are a consistent and defining feature of SAA and VSAA. Clonal expansion of Th1 cells is likely to be antigen driven and the presence of dysfunctional Tregs aggravates this autoimmune response. Increases of Tregs, and Th2/Treg ratios following IST predicts a favourable response to this treatment. Disclosures: No relevant conflicts of interest to declare.

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.

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

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