Galectin-9 expression correlates with efficacy of tacrolimus therapy in rheumatoid arthritis

2020 ◽  
Author(s):  
qiang shu ◽  
Jiao Sun ◽  
Yameng Sui ◽  
Yunqing Wang ◽  
Lijun Song ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Disease Activity ◽  
T Regulatory Cells ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
T Cell Subsets ◽  
Poor Responders ◽  
Immunological Parameters ◽  
Peripheral Blood Mononuclear

Abstract Background: The calcineurin inhibitor tacrolimus (TAC) is the second-line treatment for rheumatoid arthritis (RA). Galectin-9 (Gal-9) is a multifunctional immunomodulatory factor highly expressed in RA synovial tissues and synovial fluid. This study aimed to investigate the expression of Gal-9 and its correlation with disease activity and response to TAC in RA patients.Methods: Active RA patients were enrolled and treated with TAC alone or in combination with methotrexate and/or prednisone for 12 weeks in a prospective cohort study. Clinical and immunological parameters were recorded at baseline and at week 12. We measured Gal-9 expression in different subsets of peripheral blood mononuclear cells using flow cytometry and assayed Gal-9 levels in plasma. We also tested cytokine levels in plasma by ELISA. Results: The disease activity of RA patients notably decreased after TAC treatment. At baseline, the percentages of CD4+ T cells and T regulatory cells (CD4+CD25+CD127low) expressing Gal-9 were higher in the group with severe disease than in mild or moderate groups. After TAC treatment in RA patients, the Gal-9 expression in CD3+, CD4+, CD8+ and CD4-CD8- cell subsets decreased, as well as Gal-9 mean fluorescence intensity in CD3+, CD4+ and CD8+ T cells. Similarly, plasma Gal-9 levels were lower at week 12 than at baseline. Good responders showed significantly lower Gal-9 expression on CD3+ and CD4+ T cell subsets as well as lower plasma Gal-9 levels than poor responders. Gal-9 expression positively correlates with disease activity in RA patients.Conclusion: Gal-9 can be regarded as a new biomarker for evaluating RA activity and efficacy of TAC.

scholarly journals Galectin-9 expression correlates with therapeutic effect in rheumatoid arthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jiao Sun ◽  
Yameng Sui ◽  
Yunqing Wang ◽  
Lijun Song ◽  
Dong Li ◽  
...  
Keyword(s):  
T Cell ◽  
Disease Activity ◽  
Therapeutic Effect ◽  
Mean Fluorescence Intensity ◽  
Therapeutic Response ◽  
Severe Disease ◽  
T Cell Subsets ◽  
Poor Responders ◽  
Lower Plasma ◽  
Immunological Parameters

AbstractGalectin-9 (Gal-9) is a multifunctional immunomodulatory factor highly expressed in RA. This study aimed to investigate the expression of Gal-9 and its correlation with disease activity and therapeutic response in RA patients. Active RA patients were enrolled and treated with tacrolimus (TAC) alone or in combination therapy for 12 weeks in a prospective cohort study. Clinical and immunological parameters were recorded at baseline and week 12. We measured Gal-9 expression in different T cell subsets and in plasma. The disease activity of RA patients decreased after treatment. At baseline, the Gal-9 expression percentage was higher in the group with severe disease than in mild or moderate groups. After treatment, the Gal-9 expression in CD3+, CD4+, CD8+ and CD4-CD8− cell subsets decreased, as well as Gal-9 mean fluorescence intensity in CD3+, CD4+ and CD8+ T cells. Similarly, plasma Gal-9 levels were lower at week 12 than at baseline. Good responders showed significantly lower Gal-9 expression on CD3+ and CD4+ T cell subsets and lower plasma Gal-9 levels than poor responders. Gal-9 expression positively correlates with disease activity in RA patients. Gal-9 can be regarded as a new biomarker for evaluating RA activity and therapeutic effect, including TAC.

scholarly journals AB0044 ESTABLISHED RHEUMATOID ARTHRITIS PATIENTS HAVE INCREASED FREQUENCIES OF FOLLICULAR REGULATORY T CELLS IN PERIPHERAL BLOOD

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1325.3-1325
Author(s):  
C. Tomé ◽  
S. C. Barreira ◽  
P. Martins ◽  
A. Valido ◽  
R. Barros ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
T Cell Subsets ◽  
Peripheral Blood Mononuclear ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Healthy Donors ◽  
Cd69 Expression

Background:Several studies have demonstrated that an immune dysregulation affecting both B and T cells occurs in rheumatoid arthritis (RA). Follicular helper T (Tfh) cells are crucial for B cell maturation, activation and class-switching as well as for germinal center (GC) formation, whereas follicular regulatory T (Tfr) cells can modulate the GC reaction by suppressing Tfh and B cells.Objectives:The main goal of this study was to analyze the phenotype and frequency of circulating follicular T cell subsets in established RA patients.Methods:Blood samples were collected from established RA patients with active disease, treated with methotrexate (n=32) and from a group of age and sex-matched healthy donors (n=11). Peripheral blood mononuclear cells (PBMC) were isolated and Tfh (CD4+CXCR5+CD45RO+) and Tfr (CD4+ CXCR5+CD25+FoxP3+) cells, as well as their three major subsets [CXCR3+CCR6- (Th1-like), CXCR3-CCR6- (Th2-like) and CXCR3-CCR6+ (Th17-like)] were evaluated by flow cytometry.Results:The frequency of circulating Tfh cells was similar between established RA patients and controls. Nonetheless, RA patients had a decreased frequency of Th1-like Tfh cells, and an increased frequency of Th2-like Tfh cells when compared to controls. No significant differences were observed in the frequencies of Th17-like Tfh cells between both groups. The frequency of circulating Tfr cells was significantly increased in RA patients in comparison to controls. Furthermore, Tfr cells from RA patients had significantly increased CD69 median fluorescence intensity (MFI) values when compared to controls. No significant differences were found in the percentages and MFI values of PD-1, ICOS, CD28, CTLA-4, CD40-L and HLA-DR expressed by Tfh and Tfr cells in RA patients when compared to controls.Conclusion:Established RA patients have increased circulating frequencies of Tfr cells, with higher CD69 expression levels, when compared to healthy controls. These results suggest a pre-activation state of Tfr cells in RA and a potential role in the disease physiopathology.*RA Moura, JE Fonseca and L Graca are joint senior authors.Disclosure of Interests:None declared

scholarly journals Citrus/Cydonia Comp. Can Restore the Immunological Balance in Seasonal Allergic Rhinitis-Related Immunological Parameters In Vitro

2008 ◽  
Vol 2008 ◽  
pp. 1-5 ◽  
Author(s):  
E. W. Baars ◽  
H. F. J. Savelkoul
Keyword(s):  
T Cells ◽  
Allergic Rhinitis ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
T Cell Subsets ◽  
Immunological Parameters ◽  
Peripheral Blood Mononuclear ◽  
Selective Effect ◽  
Stimulation Of

In two in vitro studies, we examined the immunological (pathways of the) effects of Citrus/Cydonia comp. from, respectively, a healthy and an allergic donor; peripheral blood mononuclear cells (PBMCs) were isolated out of peripheral blood and analyzed in vitro after polyclonal stimulation of T-cells. The differentiation capacity and the influence with regard to Th1 (IFN-γ) and Th2 (IL-5) cells were examined. Citrus/Cydonia comp. has a selective effect on the differentiation of T-cells by producing relatively more IL-10 than IL-12. By that, it also seems to have an effect on the induction of regulatory (IL-10 producing) T-cell subsets. It is in vitro capable of neutralizing (to some extent) the changes, characteristic to allergic rhinitis, with regard to the maturation, differentiation, and activity of the immune system. Thus, Citrus/Cydonia comp. can potentially restore the disturbed immune state of rhinitis patients, which essentially could be sufficient to make allergic symptoms disappear permanently.

scholarly journals Immunomodulatory Effects of Human Adipose Tissue-derived Mesenchymal Stem Cells on T Cell Subsets in Patients with Rheumatoid Arthritis

2019 ◽  
Author(s):  
Rasoul Baharlou ◽  
Nesa Rashidi ◽  
Abbas Ahmadi-Vasmehjani ◽  
Mahshid Khoubyari ◽  
Maryam Sheikh ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Transcription Factors ◽  
T Cell ◽  
Mononuclear Cells ◽  
Orphan Receptor ◽  
T Cell Subsets ◽  
Peripheral Blood Mononuclear

Adipose-derived mesenchymal stem cells (Ad-MSCs) have been reported to suppress the effector T cell responses and have beneficial effects on various immune disorders, like rheumatoid arthritis (RA). This study was designed to investigate the effects of co-cultured Ad-MSCs on peripheral blood mononuclear cells (PBMCs) of RA patients and healthy individuals, through assessing transcription factors of T cell subsets. PBMCs from RA patients and healthy donors were co-cultured with Ad-MSCs with or without Phytohaemagglutinin (PHA). The quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of T-box 21 (T-bet), GATA-binding protein-3 (GATA3), retinoid-related orphan receptor γt (ROR-γt) and forkhead box P3 (Foxp3). Based on the results, Ad-MSCs greatly upregulated Th2 and Treg cell transcription factors, i.e., GATA3 and Foxp3 (p<0.05), and downregulated Th1 and Th17 transcription factors, i.e., T-bet and RORγt (p<0.05). These results demonstrate that Ad-MSCs can result in an immunosuppressive environment through inhibition of pro-inflammatory T cells and induction of T cells with a  regulatory phenotype. Therefore, they might have important clinical implications for inflammatory and autoimmune diseases such as RA.

scholarly journals Multiple sclerosis patients have reduced resting and increased activated CD4+CD25+FOXP3+T regulatory cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nirupama D. Verma ◽  
Andrew D. Lam ◽  
Christopher Chiu ◽  
Giang T. Tran ◽  
Bruce M. Hall ◽  
...  
Keyword(s):  
T Cells ◽  
T Regulatory Cells ◽  
Mononuclear Cells ◽  
Effector Memory ◽  
Regulatory Cells ◽  
Peripheral Blood Mononuclear ◽  
Healthy Donors ◽  
Treg Population ◽  
Multiple Sclerosis Patients ◽  
Population Iii

AbstractResting and activated subpopulations of CD4+CD25+CD127loT regulatory cells (Treg) and CD4+CD25+CD127+ effector T cells in MS patients and in healthy individuals were compared. Peripheral blood mononuclear cells isolated using Ficoll Hypaque were stained with monoclonal antibodies and analysed by flow cytometer. CD45RA and Foxp3 expression within CD4+ cells and in CD4+CD25+CD127loT cells identified Population I; CD45RA+Foxp3+, Population II; CD45RA−Foxp3hi and Population III; CD45RA−Foxp3+ cells. Effector CD4+CD127+ T cells were subdivided into Population IV; memory /effector CD45RA− CD25−Foxp3− and Population V; effector naïve CD45RA+CD25−Foxp3−CCR7+ and terminally differentiated RA+ (TEMRA) effector memory cells. Chemokine receptor staining identified CXCR3+Th1-like Treg, CCR6+Th17-like Treg and CCR7+ resting Treg. Resting Treg (Population I) were reduced in MS patients, both in untreated and treated MS compared to healthy donors. Activated/memory Treg (Population II) were significantly increased in MS patients compared to healthy donors. Activated effector CD4+ (Population IV) were increased and the naïve/ TEMRA CD4+ (Population V) were decreased in MS compared to HD. Expression of CCR7 was mainly in Population I, whereas expression of CCR6 and CXCR3 was greatest in Populations II and intermediate in Population III. In MS, CCR6+Treg were lower in Population III. This study found MS is associated with significant shifts in CD4+T cells subpopulations. MS patients had lower resting CD4+CD25+CD45RA+CCR7+ Treg than healthy donors while activated CD4+CD25hiCD45RA−Foxp3hiTreg were increased in MS patients even before treatment. Some MS patients had reduced CCR6+Th17-like Treg, which may contribute to the activity of MS.

scholarly journals OP0033 REGULATORY T CELL CD39 EXPRESSION AS A PREDICTOR OF EARLY REMISSION-INDUCTION WITH METHOTREXATE IN NEW-ONSET RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 18.2-18
Author(s):  
P. Brown ◽  
A. Anderson ◽  
B. Hargreaves ◽  
A. Morgan ◽  
J. D. Isaacs ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Disease Modifying Therapy ◽  
Blood Mononuclear Cells ◽  
Treatment Naïve ◽  
Disease Modifying ◽  
Pre Treatment

Background:The long term outcomes for patients with rheumatoid arthritis (RA) depend on early and effective disease control. Methotrexate remains the key first line disease modifying therapy for the majority of patients, with 40% achieving an ACR50 on monotherapy(1). There are at present no effective biomarkers to predict treatment response, preventing effective personalisation of therapy. A putative mechanism of action of methotrexate, the potentiation of anti-inflammatory adenosine signalling, may inform biomarker discovery. By antagonism of the ATIC enzyme in the purine synthesis pathway, methotrexate has been proposed to increase the release of adenosine moieties from cells, which exert an anti-inflammatory effect through interaction with ADORA2 receptors(2). Lower expression of CD39 (a cell surface 5-’ectonucleotidase required for the first step in the conversion of ATP to adenosine) on circulating regulatory T-Lymphocytes (Tregs) was previously identified in patients already established on methotrexate who were not responding (DAS28 >4.0 vs <3.0)(3). We therefore hypothesised that pre-treatment CD39 expression on these cells may have clinical utility as a predictor of early methotrexate efficacy.Objectives:To characterise CD39 expression in peripheral blood mononuclear cells in RA patients naïve to disease modifying therapy commencing methotrexate, and relate this expression to 4 variable DAS28CRP remission (<2.6) at 6 months.Methods:68 treatment naïve early RA patients starting methotrexate were recruited from the Newcastle Early Arthritis Clinic and followed up for 6 months. Serial blood samples were taken before and during methotrexate therapy with peripheral blood mononuclear cells isolated by density centrifugation. Expression of CD39 by major immune subsets (CD4+ and CD8+ T-cells, B-lymphocytes, natural killer cells and monocytes) was determined by flow cytometry. The statistical analysis used was binomial logistic regression with baseline DAS28CRP used as a covariate due to the significant association of baseline disease activity with treatment response.Results:Higher pre-treatment CD39 expression was observed in circulating CD4+ T-cells of patients who subsequently achieved clinical remission at 6 months versus those who did not (median fluorescence 4854.0 vs 3324.2; p = 0.0108; Figure 1-A). This CD39 expression pattern was primarily accounted for by the CD4+CD25 high sub-population (median fluorescence 9804.7 vs 6455.5; p = 0.0065; Figure 1-B). These CD25 high cells were observed to have higher FoxP3 and lower CD127 expression than their CD39 negative counterparts, indicating a Treg phenotype. No significant associations were observed with any other circulating subset. A ROC curve demonstrates the discriminative utility of differential CD39 expression in the CD4+CD25 high population for the prediction of DAS28CRP remission in this cohort, showing greater specificity than sensitivity for remission prediction(AUC: 0.725; 95% CI: 0.53 - 0.92; Figure 1-C). Longitudinally, no significant induction or suppression of the CD39 marker was observed amongst patients who did or did not achieve remission over the 6 months follow-up period.Figure 1.Six month DAS28CRP remission versus pre-treatment median fluorescence of CD39 expression on CD4+ T-cells (A); CD25 High expressing CD4+ T-cells (B); and ROC curve of predictive utility of pre-treatment CD39 expression on CD25 High CD4+ T-cells (C).Conclusion:These findings support the potential role of CD39 in the mechanism of methotrexate response. Expression of CD39 on circulating Tregs in treatment-naïve RA patients may have particular value in identifying early RA patients likely to respond to methotrexate, and hence add value to evolving multi-parameter discriminatory algorithms.References:[1]Hazlewood GS, et al. BMJ. 2016 21;353:i1777[2]Brown PM, et al. Nat Rev Rheumatol. 2016;12(12):731-742[3]Peres RS, et al. Proc Natl Acad Sci U S A. 2015;112(8):2509-2514Disclosure of Interests:None declared

scholarly journals Single-cell multi-omics analysis of the immune response in COVID-19

2021 ◽  
Author(s):  
Emily Stephenson ◽  
◽  
Gary Reynolds ◽  
Rachel A. Botting ◽  
Fernando J. Calero-Nieto ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Single Cell ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Effector Memory ◽  
Peripheral Blood Mononuclear ◽  
Cross Sectional ◽  
Hematopoietic Stem ◽  
Symptomatic Disease

AbstractAnalysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.

Increased Serum Interleukin 22 in Patients with Rheumatoid Arthritis and Correlation with Disease Activity

2012 ◽  
Vol 39 (7) ◽  
pp. 1320-1325 ◽  
Author(s):  
LAURINDO FERREIRA da ROCHA ◽  
ÂNGELA LUZIA BRANCO PINTO DUARTE ◽  
ANDRÉA TAVARES DANTAS ◽  
HENRIQUE ATAÍDE MARIZ ◽  
IVAN da ROCHA PITTA ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Mononuclear Cells ◽  
Activity Index ◽  
Elevated Serum ◽  
Serum Levels ◽  
Peripheral Blood Mononuclear ◽  
Additional Tool ◽  
Bone Erosions ◽  
Interleukin 22

Objective.To analyze the role of interleukin 22 (IL-22) in rheumatoid arthritis (RA).Methods.IL-22 serum levels were measured in 83 patients with established RA under treatment with disease-modifying antirheumatic drugs and in 30 healthy controls matched for age and sex. Patients were assessed for clinical and laboratory variables. Correlations of IL-22 serum levels with disease activity measures [Clinical Disease Activity Index (CDAI) and Disease Activity Score for 28 joints (DAS28)], serological markers, bone erosions, and demographic factors were assessed. Peripheral blood mononuclear cells (PBMC) from 30 patients with RA and 14 controls were purified and stimulatedin vitrowith phorbol myristate acetate (PMA)/ionomycin. IL-22 production by PBMC and in serum was investigated by ELISA.Results.IL-22 levels were increased in patients with RA compared with controls (mean 432.37 pg/ml and 67.45 pg/ml, respectively; p < 0.001). Levels of IL-22 correlated with DAS28 and CDAI measures. Rheumatoid factor (RF) positivity was correlated with higher levels of IL-22 in patients with RA (mean 575.08 pg/ml; p = 0.001). The presence of bone erosions was associated with high IL-22 levels (p = 0.0001). PBMC stimulated with PMA/ionomycin expressed higher levels of IL-22 in patients with RA than controls but this was not significant (mean 584.75 pg/ml and 295.57 pg/ml; p = 0.553).Conclusion.IL-22 is elevated in the serum of patients with established RA. Elevated serum IL-22 allows discrimination between patients with different clinical and laboratory measures and indicates the potential of IL-22 as an additional tool for assessment of activity in RA, particularly in patients with RF antibodies and longterm disease. IL-22 is associated with bone-destructive disease.

Abstract 425: Lycopene Modulates T Lymphocyte Function by Modulating Th1 Responses and Treg Lymphocyte Population

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Lynsey M Mills ◽  
Heather Wilson ◽  
Frank Thies
Keyword(s):  
T Lymphocyte ◽  
T Regulatory Cells ◽  
Mononuclear Cells ◽  
T Cell Subsets ◽  
Lymphocyte Function ◽  
T Helper ◽  
T Helper 1 ◽  
Peripheral Blood Mononuclear ◽  
Lymphocyte Activity ◽  
Ifn Γ

Increased lycopene intake might have cardiovascular benefits, potentially through anti-inflammatory mechanisms. We recently showed that lycopene can influence lymphocyte activity by modulating processes involved in early cellular activation. T lymphocytes comprise different subsets, T cytotoxic, T helper 1 (Th1), T helper 2 (Th2) and T regulatory cells (Treg). We aimed to determine whether lycopene could specifically modulate T-cell subsets function and activity. Peripheral blood mononuclear cells from 11 healthy adults were cultured for 18hr to 60h in the presence of lycopene-enriched liposomes (0-1.18μg lycopene/ml) with or without mitogens. The secretion of cytokines representative of Th1,Th2 and Treg activities were measured by ELISA (IL-2, IL-1β, IL-10, IFN-γ and TGF-β) or cytometric bead array (IL-4, IL-10, IL17 and IFN-γ). The population profile of Tc (CD3+/CD8+), Th (CD3+/CD4+), Treg (CD4+/CD25+), and the Treg subsets nTreg (CD4+/CD25+/FoxP3+) and iTreg (CD4+/CD25+/IL-10+) was determined by flow cytometry. After 18h incubation, IL-2 concentration in the medium was significantly reduced (-29%, p=0.001) in the presence of lycopene (1.18μg/mL). Similar effects were observed after 36h and 60h culture for IFN-γ (-23%, p=0.015), Il-10 (-30%, p=0.023), IL-17 (-30%, p=0.019) but not IL-4 or TGF-β. The proportion of Treg cell was also significantly increased by 36% (p=0.001) in the presence of lycopene (1.18μg/mL) compared with non-treated activated cells. Furthermore, the proportions of iTreg cells were significantly increased by after incubation with lycopene while the proportion of nTreg cells decreased (-20.5 %, p=0.049). We conclude that increased lycopene intake may be beneficial against atherogenesis by modulating T lymphocyte function, particularly in relation toTh1 and Treg.

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