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.

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 Sex-based differences in association between circulating T cell subsets and disease activity in untreated early rheumatoid arthritis patients

2018 ◽  
Vol 20 (1) ◽  
Author(s):  
Jonathan Aldridge ◽  
Jayesh M. Pandya ◽  
Linda Meurs ◽  
Kerstin Andersson ◽  
Inger Nordström ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
T Cell Subsets

Childhood multiple sclerosis: Clinical features and demonstration of changes in T cell subsets with disease activity

1982 ◽  
Vol 11 (5) ◽  
pp. 463-468 ◽  
Author(s):  
Stephen L. Hauser ◽  
Michael J. Bresnan ◽  
Ellis L. Reinherz ◽  
Howard L. Weiner
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Disease Activity ◽  
Clinical Features ◽  
T Cell Subsets

scholarly journals CD3+CD4+gp130+ T Cells Are Associated With Worse Disease Activity in Systemic Lupus Erythematosus Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Nur Diyana Mohd Shukri ◽  
Aziz Farah Izati ◽  
Wan Syamimee Wan Ghazali ◽  
Che Maraina Che Hussin ◽  
Kah Keng Wong
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Lymphocyte Subpopulations ◽  
Gene Set Enrichment Analysis ◽  
T Cell Subsets ◽  
Healthy Controls ◽  
Systemic Lupus

The receptors for IL-35, IL-12Rβ2 and gp130, have been implicated in the inflammatory pathophysiology of autoimmune diseases. In this study, we set out to investigate the serum IL-35 levels and the surface levels of IL-12Rβ2 and gp130 in CD3+CD4+, CD3+CD4─ and CD3─CD4─ lymphocyte subpopulations in systemic lupus erythematosus (SLE) patients (n=50) versus healthy controls (n=50). The potential T cell subsets associated with gp130 transcript (i.e. IL6ST) expression in CD4+ T cells of SLE patients was also examined in publicly-available gene expression profiling (GEP) datasets. Here, we report that serum IL-35 levels were significantly higher in SLE patients than healthy controls (p=0.038) but it was not associated with SLEDAI-2K scores. The proportions of IL-12Rβ2+ and gp130+ cells in SLE patients did not differ significantly with those of healthy controls in all lymphocyte subpopulations investigated. Essentially, higher SLEDAI-2K scores were positively correlated with increased proportion of gp130+ cells, but not IL-12Rβ2+ cells, on CD3+CD4+ T cells (r=0.425, p=0.002, q=0.016). Gene Set Enrichment Analysis (GSEA) of a GEP dataset of CD4+ T cells isolated from SLE patients (n=8; GSE4588) showed that IL6ST expression was positively associated with genes upregulated in CD4+ T cells vs myeloid or B cells (q<0.001). In an independent GEP dataset of CD4+ T cells isolated from SLE patients (n=9; GSE1057), IL6ST expression was induced upon anti-CD3 stimulation, and that Treg, TCM and CCR7+ T cells gene sets were significantly enriched (q<0.05) by genes highly correlated with IL6ST expression (n=92 genes; r>0.75 with IL6ST expression) upon anti-CD3 stimulation in these SLE patients. In conclusion, gp130 signaling in CD3+CD4+ T cell subsets may contribute to increased disease activity in SLE patients, and it represents a promising therapeutic target for inhibition in the disease.

scholarly journals Value of Immunological Markers in Predicting Responsiveness to Influenza Vaccination in Elderly Individuals

2001 ◽  
Vol 75 (24) ◽  
pp. 12182-12187 ◽  
Author(s):  
Jörg J. Goronzy ◽  
James W. Fulbright ◽  
Cynthia S. Crowson ◽  
Gregory A. Poland ◽  
William M. O'Fallon ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Biological Markers ◽  
Cell Subset ◽  
Influenza Virus Vaccine ◽  
Antibody Responses ◽  
T Cell Subsets ◽  
Immunological Parameters ◽  
Elderly Individuals

ABSTRACT Elderly individuals are at high risk for morbidity and mortality when infected with influenza virus. Vaccinations with inactivated virus are less effective in the elderly due to the declining competency of the aging immune system. We have explored whether immunological parameters predict poor anti-influenza virus vaccine responses and can be used as biological markers of immunosenescence. One hundred fifty-three residents of community-based retirement facilities aged 65 to 98 years received a trivalent influenza vaccine. Vaccine-induced antibody responses were determined by comparing hemagglutination inhibition titers before and 28 days after immunization. The composition of the T-cell compartment was analyzed by flow cytometry and the sizes of three T-cell subsets, CD4+CD45RO+ cells, CD4+ CD28null cells, and CD8+ CD28null cells, were determined. Only 17% of the vaccine recipients were able to generate an increase in titers of antibody to all three vaccine components, and 46% of the immunized individuals failed to respond to any of the three hemagglutinins. The likelihood of successful vaccination declined with age and was independently correlated with the expansion of a particular T-cell subset, CD8+ CD28null T cells. The sizes of the CD4+ CD45RO+ memory T-cell and CD4+ CD28null T-cell subsets had no effect on the ability to mount anti-influenza virus antibody responses. Frequencies of CD8+ CD28null T cells are useful biological markers of compromised immunocompetence, identifying individuals at risk for insufficient antibody responses.

scholarly journals The induction of experimental autoimmune myocarditis in mice lacking CD4 or CD8 molecules [corrected]

1993 ◽  
Vol 178 (5) ◽  
pp. 1837-1842 ◽  
Author(s):  
J M Penninger ◽  
N Neu ◽  
E Timms ◽  
V A Wallace ◽  
D R Koh ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Severe Disease ◽  
Heart Tissue ◽  
T Cell Subsets ◽  
Autoimmune Myocarditis ◽  
Cd8 Cells ◽  
Organ Specific

Experimental induction of most autoimmune diseases appears to depend on the activation of CD4+ T helper cells, while CD8+ lymphocytes may have a role in disease progression. To study the role of CD4+ and CD8+ T cell subsets in T cell-dependent autoimmunity, mice lacking CD4 or CD8 molecules after gene targeting were injected with cardiac myosin to induce organ specific autoimmune myocarditis. Mice homozygous for the CD8 mutation (CD8-/-) developed significantly more severe disease as compared to CD4+/-CD8+/- controls. Surprisingly, CD4-/- mice developed autoimmune myocarditis with infiltration of TCR alpha beta +CD4-CD8- T cells in the heart tissue and appearance of autoantibodies. These data demonstrate that the lack of CD4+ or CD8+ T cells has no significant influence on the initiation of autoimmune myocarditis. CD4+ and CD8+ cells regulate disease severity and these results may explain the occurrence of autoimmunity in CD4 immunodeficiencies.

scholarly journals NK and T Cell Immunological Signatures in Hospitalized Patients with COVID-19

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3182
Author(s):  
Laura Bergantini ◽  
Miriana d'Alessandro ◽  
Paolo Cameli ◽  
Dalila Cavallaro ◽  
Sara Gangi ◽  
...  
Keyword(s):  
T Cell ◽  
Nk Cells ◽  
Viral Infections ◽  
Nk Cell ◽  
Severe Disease ◽  
Clinical Severity ◽  
T Cell Subsets ◽  
Adaptive Memory ◽  
Parallel Increase ◽  
Hospitalised Patients

Severe acute respiratory syndrome caused by coronavirus 2 emerged in Wuhan (China) in December 2019 and has severely challenged the human population. NK and T cells are involved in the progression of COVID-19 infection through the ability of NK cells to modulate T-cell responses, and by the stimulation of cytokine release. No detailed investigation of the NK cell landscape in clinical SARS-CoV-2 infection has yet been reported. A total of 35 COVID-19 hospitalised patients were stratified for clinical severity and 17 healthy subjects were enrolled. NK cell subsets and T cell subsets were analysed with flow cytometry. Serum cytokines were detected with a bead-based multiplex assay. Fewer CD56dimCD16brightNKG2A+NK cells and a parallel increase in the CD56+CD69+NK, CD56+PD-1+NK, CD56+NKp44+NK subset were reported in COVID-19 than HC. A significantly higher adaptive/memory-like NK cell frequency in patients with severe disease than in those with mild and moderate phenotypes were reported. Moreover, adaptive/memory-like NK cell frequencies were significantly higher in patients who died than in survivors. Severe COVID-19 patients showed higher serum concentrations of IL-6 than mild and control groups. Direct correlation emerged for IL-6 and adaptive/memory-like NK. All these findings provide new insights into the immune response of patients with COVID-19. In particular, they demonstrate activation of NK through overexpression of CD69 and CD25 and show that PD-1 inhibitory signalling maintains an exhausted phenotype in NK cells. These results suggest that adaptive/memory-like NK cells could be the basis of promising targeted therapy for future viral infections.

scholarly journals Regulatory T Cells as Predictors of Clinical Course in Hospitalised COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Sara Caldrer ◽  
Cristina Mazzi ◽  
Milena Bernardi ◽  
Marco Prato ◽  
Niccolò Ronzoni ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Clinical Course ◽  
Severe Disease ◽  
Clinical Severity ◽  
T Cell Subsets ◽  
Cell Subpopulation ◽  
Phenotypic Analysis ◽  
Clinical Evolution

BackgroundThe host immune response has a prominent role in the progression and outcome of SARS-CoV-2 infection. Lymphopenia has been described as an important feature of SARS-CoV-2 infection and has been associated with severe disease manifestation. Lymphocyte dysregulation and hyper-inflammation have been shown to be associated with a more severe clinical course; however, a T cell subpopulation whose dysfunction correlate with disease progression has yet to be identify.MethodsWe performed an immuno-phenotypic analysis of T cell sub-populations in peripheral blood from patients affected by different severity of COVID-19 (n=60) and undergoing a different clinical evolution. Clinical severity was established based on a modified WHO score considering both ventilation support and respiratory capacity (PaO2/FiO2 ratio). The ability of circulating cells at baseline to predict the probability of clinical aggravation was explored through multivariate regression analyses.ResultsThe immuno-phenotypic analysis performed by multi-colour flow cytometry confirmed that patients suffering from severe COVID-19 harboured significantly reduced circulating T cell subsets, especially for CD4+ T, Th1, and regulatory T cells. Peripheral T cells also correlated with parameters associated with disease severity, i.e., PaO2/FiO2 ratio and inflammation markers. CD4+ T cell subsets showed an important significant association with clinical evolution, with patients presenting markedly decreased regulatory T cells at baseline having a significantly higher risk of aggravation. Importantly, the combination of gender and regulatory T cells allowed distinguishing between improved and worsened patients with an area under the ROC curve (AUC) of 82%.ConclusionsThe present study demonstrates the association between CD4+ T cell dysregulation and COVID-19 severity and progression. Our results support the importance of analysing baseline regulatory T cell levels, since they were revealed able to predict the clinical worsening during hospitalization. Regulatory T cells assessment soon after hospital admission could thus allow a better clinical stratification and patient management.

scholarly journals Immune Status Against Hepatitis B in Patients After Allogeneic Hematopoietic Cell Transplantation—Factors Affecting Early and Long-Lasting Maintenance of Protective Anti-HBs Titers

2020 ◽  
Vol 11 ◽  
Author(s):  
Agnieszka Piekarska ◽  
Piotr Wisniewski ◽  
Krzysztof Lewandowski ◽  
Lidia Gil ◽  
Piotr Trzonkowski ◽  
...  
Keyword(s):  
T Cell ◽  
Hepatitis B ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hepatitis B Surface Antigen ◽  
Vaccination Schedule ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
T Cell Subsets ◽  
Immunological Parameters

The immunization of allogeneic hematopoietic cell transplantation (HCT) recipients against vaccine-preventable diseases is a part of posttransplantation guidelines. We conducted a prospective study to assess clinical and immunological parameters that would determine the response and long-term maintenance of protective antibody titers upon the hepatitis B virus (HBV) vaccination after HCT. The investigated variables included: vaccination of the HCT recipients and their donors prior to HCT, chronic graft versus host disease (cGVHD) and the timing of post-HCT vaccination, and B- and T-cell subtype status. Forty-two patients were immunized with three or more doses of recombinant hepatitis B surface antigen (rHBsAg) administered according to the individualized schedule of 0-1-2-6-(12) months. After vaccination, seroconversion was achieved in the whole group. The vaccines were categorized according to the antibody (Ab) titers as weak (WRs; 28.7%), good (GRs; 38%) or very good responders (VGRs; 3.3%). In multivariate logistic regression, severe cGVHD (OR= 15.5), and preceding donor immunization (OR= 0.13) were independent predictors of a weak response to vaccination. A prior belonging to the WR group impaired the durability of protection (OR= 0.17) at a median follow-up of 11.5 years. Patients with severe cGVHD showed a trend toward lower median Ab titers, although they required a higher rate of booster vaccine doses. All VGRs had CD4+ cells > 0.2 x 106/L. There was a lower mean rate of CD4+IL2+ lymphocytes in WRs. Vaccination demonstrated the immunomodulatory effect on B-cell and T-cell subsets and a Th1/Th2 cytokine profile, while shifts depended on a history of severe cGVHD and the type of vaccine responder. To conclude, vaccination of HCT donors against HBV allows a better response to vaccination in the respective HCT recipients. Double doses of rHBsAg should be considered in patients with cGVHD and in those not immunized before HCT. A dedicated intensified vaccination schedule should be administered to WRs.

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