AB0043 THE IMBALANCE OF T FOLLICULAR REGULATORY CELL AND T FOLLICULAR HELPER CELL IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1324-1325
Author(s):  
R. Su ◽  
Y. Y. Wang ◽  
F. Y. Hu ◽  
X. Zheng ◽  
Y. Liu ◽  
...  

Background:Rheumatoid arthritis (RA) is a chronic inflammatory disease which can lead to severe joint damage and disability.The relationship between antibodies and rheumatoid arthritis has long been well established. Recently, many studies have found that T follicular regulatory cells(Tfr) and T follicular helper cells (Tfh) are closely related to antibody generation on lymphoid follicular germinal centers (GCs)[1-2]. Tfr cells can inhibite the GC reaction and suppress production of high-affinity antibodies. The dysregulation of Tfh cells can lead to the production of autoantibodies by B cells.Objectives:To examine the expression of circulating T follicular regulatory cell (Tfr) and T follicular helper cell and its subsets(Tfh1 Tfh2 Tfh17) in RA patients and healthy control group.Methods:Level of Tfr and Tfh1,Tfh2 and Tfh17 cells in the peripheral blood of 17 new RA patients, 30 treated RA patients and 18 healthy controls were deceted by flow cytomery. All patients were hospitalised at the Department of Rheumatology, Second Hospital of Shanxi Medical University.Results:We found that the level of Tfr (CD3+CD4+CD25+CXCR5+FOP3+) percent(P=0.020), in the peripheral blood in RA patients were significantly decreased compared with healthy controls. The percent of Tfh (CD3+CD4+CXCR5+CD45RA-) (P=0.039)and Tfh17 (CD3+CD4+CXCR5+CD45RA-CXCR3-CCR6+) (P=0.000)were increased, but there are no statistical difference about Tfh1(CD3+CD4+CXCR5+CD45RA-CXCR3+CCR6-)(P=0.558) and Tfh2 (CD3+CD4+CXCR5+CD45RA-CXCR3-CCR6-) percent(P=0.079). We compared the above indicators between new and treated RA patients, and the results indicated that the Tfr(P=0.013),Tfh (P=0.002) and Tfh1(P=0.034) were significantly increased in the new RA patients compared to the treated RA patients, there were no differences between the two groups in Tfh2(P=0.419) and Tfh17 percent(P=0.124).Conclusion:Our results indicated that disorder of Tfr and Tfh subsets were involved in RA, restoring the Tfr/Tfh balance may be the potential therapeutic targets.Fig. 1.Comparison of Tfr, Tfh and its subsets(Tfh1 Tfh2 Tfh17) percent among the RA patients (n = 47) and healthy control group (n = 18) (*P < 0.05).Fig. 2.Comparison of Tfr,Tfh and its subsets(Tfh1 Tfh2 Tfh17) percent among the new RA patients (n = 17) and treated RA patients(n = 30) (*P < 0.05).References:[1]Deng J, Wei Y, Fonseca VR, Graca L, Yu D.T follicular helper cells and T follicular regulatory cells in rheumatic diseases[J].Nat Rev Rheumatol. 2019, 15(8):475-490.[2]Chen Liu, Dongwei Wang, Songsong Lu, et al.Increased Circulating Follicular Treg Cells Are Associated With Lower Levels of Autoantibodies in Patients With Rheumatoid Arthritis in Stable Remission.Arthritis Rheumatol. 2018, 70(5):711-721Disclosure of Interests:None declared

2021 ◽  
Author(s):  
Yasemin Gider ◽  
Xhariga Jabbarli ◽  
Gamze Uyaroglu ◽  
Seref Bugra Tuncer ◽  
Demet Akdeniz Odemis ◽  
...  

Abstract Background The most common cancers detected in women are breast, thyroid, colorectal, uterine corpus, lung, and ovarian cancer. Ovarian cancer is responsible from more than 150.000 death annually worldwide. This cancer is detected in the late stage, and is characterised with poor prognosis, therefore most cases result with death. The fact that this cancer manifests itself in the late stage and is characterized by a poor prognosis, is caused death in the majority of cases. Therefore, the diagnosis and the treatment of the disease have to be improved for a better quality of life for patients. MicroRNAs are the noncoding RNAs in the length of 19–24 nucleotides which show suppressor effect on target genes. miRNAs are included in the pathology of various diseases including cancer. miRNAs being as the biomarker candidates in diagnosis, and their use in treatment as the inhibitors of the molecules mimicking the miRNA showed that they may be used as the new therapeutic target and agents. Methods We detected with our group in our prior study conducted with disconcordant ovarian cancer twins that many miRNA molecules were different in ovarian cancer compared with the molecules in healthy sibling. The expression level of miR-142-3p that was selected from the miRNAs detected in the previous study was compared, and investigated in a wider ovarian cancer group, and in healthy control group. miR-142-3p expression level was investigated using the real-time PCR method in the present study involving 147 patients, and 100 healthy control group. The differences in the expression levels of miR-142-3p detected in the peripheral blood lymphocytes of ovarian cancer patients, and healthy control were statisticaly evaluated. Results The expression level of miR-142-3p was detected to have increased 3.11 fold in ovarian cancer patients compared with the levels in healthy controls, and the difference was statistically significant (p:0.00). These results suggest that miR-142-3p that was found significantly increased in the peripheral blood samples of ovarian cancer patients compared with the healthy controls might be used as a sensitive, noninvasive biomarker in the early diagnosis, and treatment and follow up of ovarian cancer.


2021 ◽  
Author(s):  
Dornatien C Anang ◽  
Tamara H. Ramwadhdoebe ◽  
Janine Hahnlein ◽  
Bo van Kuijk ◽  
Noortje Smits ◽  
...  

Objectives: Follicular helper T cells (Tfh cells) provide key B cell help, and are essential in germinal center (GC) formation and (auto) antibody generation. To gain more insight into their role during the earliest phase of rheumatoid arthritis (RA) we analyzed their frequencies, phenotype and cytokine profile in peripheral blood and lymphoid tissues. Methods: Using flow cytometry, we studied the frequency of Tfh and B cells in peripheral blood and lymph node (LN) needle biopsies. Three donor groups were included and compared: healthy controls (HCs), autoantibody positive individuals at risk for developing RA (RA-risk individuals), and early RA patients. Ex vivo stimulation of lymphocytes with PMA/ionomycin was performed to assess cytokine secretion by Tfh cells. Results: In blood, the frequency of circular Tfh cells (cTfh) did not differ between study groups. In lymphoid tissue, the frequency of Tfh cells correlated strongly with the frequency of CD19+ B cells. Compared to healthy controls, LN samples of RA patients and RA-risk individuals showed more CD19+ B cells and more CD4+CXCR5+ and CD8+CXCR5+ Tfh cells. These Tfh cells from LNs expressed less IL-21 upon ex vivo stimulation. Conclusion: LN tissue of early RA patients as well as part of RA-risk individuals exhibit increased frequencies of Tfh cells correlating with increased numbers of B cells. Interestingly, IL-21 production is already aberrant in the very early at risk phase of the disease. This suggests that Tfh cells may present a novel rationale for therapeutic targeting during the preclinical stage of the disease to prevent further disease progression.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Baoen Jiang ◽  
Xiuqin Kang ◽  
Gang Zhao ◽  
Jianshu Lu ◽  
Zhitao Wang

Objective. To study the effect of miR-138 on the function of osteosarcoma (OS) T follicular helper cells (Tfh cells) and its mechanism. Methods. Peripheral blood mononuclear cells (PBMCs) were isolated from patients with osteosarcoma (OS group) and healthy volunteers (control group). CD4+CXCR5+ Tfh cells and CD9+ B cells were sorted by flow cytometry. qRT-PCR was used to detect the expression of miR-138 and PDK1 in the peripheral blood and CD4+CXCR5+ Tfh cells. Flow cytometry was employed to detect the proportion of CD4+CXCR5+ Tfh cells in CD4+ T cells, the level of CD40L in CD4+CXCR5+ Tfh cells, and the expression of CD27 and CD38 in B cells. Western blot was used to determine the protein expression of PDK1, PI3K, p-Akt, Akt, p-mTOR, and mTOR. In addition, dual-luciferase reporter assay was performed to verify the relationship between miR-138 and PDK1. ELISA method was used to determine the levels of IgM, IgG, IL-10, and IL-21. Results. Compared with that of the control group, the expression of miR-138 in PBMC and CD4+CXCR5+ Tfh cells of the OS group was lower; overexpression of miR-138 could promote the maturation of Tfh cells and immature B cells. The results of the dual-luciferase report experiment showed that miR-138 can target and negatively regulate PDK1, and PDK1 can reverse the effect of miR-138 on the function of Tfh cells and immature B cells. Conclusion. miR-138 inhibits the PI3K/Akt/mTOR pathway by targeting and negatively regulating PDK1 to alleviate the dysfunction of T follicular helper cells in OS.


RMD Open ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. e001485
Author(s):  
Johanna M Kroese ◽  
Catherine M C Volgenant ◽  
Wim Crielaard ◽  
Bruno Loos ◽  
Dirkjan van Schaardenburg ◽  
...  

ObjectiveTo evaluate the prevalence of temporomandibular disorders (TMD) in patients with early rheumatoid arthritis (ERA) and individuals at-risk of RA.Methods150 participants were recruited in three groups (50 per group): (1) patients with ERA (2010 EULAR criteria) (2) at-risk individuals and (3) healthy controls. All participants were tested for seropositivity of rheumatoid factor and anticitrullinated protein antibodies. A possible TMD diagnosis was determined according to the standardised and validated diagnostic criteria for TMD (DC/TMD) in five categories: myalgia, arthralgia, articular disc displacement, degenerative joint disease and headache attributed to TMD. Results were tested for the prevalence of TMD (all categories combined) and TMD pain (myalgia and/or arthralgia). To investigate a possible role for bruxism, a probable sleep and/or awake bruxism diagnosis was determined based on self-report and several clinical features.ResultsThe prevalence of any TMD diagnosis did not differ between the three groups. However, at-risk individuals more often had a TMD-pain diagnosis than healthy controls (p=0.046). No such difference was found between the ERA group and the control group. However, within the ERA group, seronegative patients had a TMD-pain diagnosis more often than seropositive patients (4/12 (33%) vs 3/38 (8%), p=0.048). Participants with a TMD-pain diagnosis were more often diagnosed with probable sleep bruxism than those without a TMD-pain diagnosis.ConclusionThe prevalence of TMD pain is increased in individuals at-risk of RA and seronegative ERA patients, and is associated with bruxism signs and symptoms. These results suggest that health professionals should be alert to TMD pain in these groups.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yan-Long Ren ◽  
Tao-Tao Li ◽  
Wei Cui ◽  
Li-Min Zhao ◽  
Na Gao ◽  
...  

AbstractInterferon-gamma (IFN-γ) is a cytokine involved in the pathogenesis of Takayasu’s arteritis (TAK). However, the source of IFN-γ in TAK patients is not fully clear. We aimed to investigate the source of IFN-γ in TAK. 60 TAK patients and 35 health controls were enrolled. The lymphocyte subsets of peripheral blood were detected by flow cytometry, cytokines were detected by Bio-plex. The correlation among lymphocyte subsets, cytokines and disease activity indexes was analyzed by person correlation. The level of serum IFN-γ in TAK patients was significantly increased (P < 0.05). The percentage of CD3+IFN-γ+ cells in peripheral blood CD3+ cells was significantly higher in TAK patients than that of healthy control group (P = 0.002). A higher proportion of CD3+CD8+IFN-γ+ cells/CD3+IFN-γ+ cells (40.23 ± 11.98% vs 35.12 ± 11.51%, P = 0.049), and a significantly lower CD3+CD4+IFN-γ+/ CD3+CD8+IFN-γ+ ratio (1.34 ± 0.62% vs 1.80 ± 1.33%, P = 0.027) were showed in the TAK group than that of control group. The CD3+CD8+IFN-γ+/CD3+IFN-γ+ ratio was positively correlated with CD3+IFN-γ+cells/ CD3+cells ratio (r = 0.430, P = 0.001), serum IFN-γ level (r = 0.318, P = 0.040) and IL-17 level (r = 0.326, P = 0.031). It was negatively correlated with CD3+CD4+IFN-γ+/CD3+IFN-γ+ ratio (r = − 0.845, P < 0.001). IFN-γ secreted by CD3+CD8 + T cells is an important source of serum IFN-γ in TAK patients.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Luisa Guidi ◽  
Carla Felice ◽  
Annabella Procoli ◽  
Giuseppina Bonanno ◽  
Enrica Martinelli ◽  
...  

Treg modulation has been hypothesized as one of the mechanisms by which antitumor necrosis factorα(TNFα) agents exert their action in rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). However, data in IBD are still conflicting. We evaluated CD4+CD25+FOXP3+(Tregs) by flow cytometry in peripheral blood from 32 adult IBD patient before (T0) and after the induction of anti-TNFαtherapy (T1). Eight healthy controls (HCs) were included. We also evaluated the number of FOXP3+cells in the lamina propria (LP) in biopsies taken in a subset of patients and controls. Treg frequencies were significantly increased in peripheral blood from our patients after anti-TNFαtherapy compared to T0. T1 but not T0 levels were higher than HC. The increase was detectable only in clinical responders to the treatment. A negative correlation was found among delta Treg levels and the age of patients or disease duration and with the activity score of Crohn’s disease (CD). No significant differences were found in LP FOXP3+cells. Our data suggest the possibility that in IBD patients the treatment with anti-TNFαmay affect Treg percentages and that Treg modifications may correlate with clinical response, but differently in early versus late disease.


2018 ◽  
Vol 94 (1111) ◽  
pp. 278-283 ◽  
Author(s):  
Xue-Feng Xie ◽  
Xiao-Hui Huang ◽  
Ai-Zong Shen ◽  
Jun Li ◽  
Ye-Huan Sun

AimLeptin, synthesised by adipocytes, has been identified as a hormone that can influence inflammatory activity. Several studies have investigated leptin levels in patients with multiple sclerosis (MS), but the results are not consistent. This study aims to derive a more precise evaluation on the relationship between circulating leptin levels and MS.DesignA comprehensive literature searched up to July 2017 was conducted to evaluate the association of circulating leptin levels and MS. The random-effect model was applied to calculate pooled standardised mean difference (SMD) and its 95% CI.Main outcome measuresCirculating leptin levels of patients with MS and healthy controls.ResultsOf 2155 studies identified, 33 met eligibility criteria and 9 studies with 645 patients with MS and 586 controls were finally included in the meta-analysis. Meta-analysis revealed that, compared with the healthy control group, the MS group had significantly higher plasma/serum leptin levels, with the SMD of 0.70% and 95% CI (0.24 to 1.15). Subgroup analyses suggested that the leptin levels of patients with MS were associated with region, age, study sample size, measurement type, gender and blood sample type.ConclusionOverall, our study suggests that patients with MS have a significantly higher leptin level than in healthy controls. Further mechanism studies and longitudinal large cohort studies are still needed to further reveal the role of leptin in the pathogenesis of MS.


2008 ◽  
Vol 66 (3b) ◽  
pp. 678-684 ◽  
Author(s):  
Soniza Vieira Alves-Leon ◽  
Maria Lucia Vellutini Pimentel ◽  
Gabrielle Sant'Anna ◽  
Fabíola Rachid Malfetano ◽  
Cláudio Duque Estrada ◽  
...  

Neuromyelitis optica (NMO) is an inflammatory, demyelinating disease of the central nervous system characterized by the association of a serious myelitis and unilateral or bilateral optic neuritis. The present study aimed to analyze the immunological parameters of NMO patients with diagnosis established based on Wingerchuck et al. (1999) criteria. Production of IgG and IgA antibodies to antigens of MBP, PLP 95-116, MOG 92-106, and the cytokines interleukin-4 (IL-4) and interferon-γ (INF-γ) were assessed by Elisa assay. The cohort was formed by 28 NMO patients and a matched healthy control group. NMO patients had significant high levels of IgG to MOG (p<0.0001), PLP (p=0.0002) and MBP (p<0.0001), and solely IgA to MBP (p<0.0001). INF-γ (p=0.61) levels were similar to healthy controls. Increased production of IL-4 (p=0.0084) indicates an important role for this cytokine in the activation of Th2 regulatory cells and of the IgA producers B lymphocyte indicating activation of humoral immunity.


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