Background:Immunosuppressive medication reduces the immunogenicity of the coronavirus disease 2019(COVID-19)vaccines in patients with rheumatic and musculoskeletal diseases(RMDs).However,the underlying mechanism remai...Background:Immunosuppressive medication reduces the immunogenicity of the coronavirus disease 2019(COVID-19)vaccines in patients with rheumatic and musculoskeletal diseases(RMDs).However,the underlying mechanism remains unclear.The primary aim of our study was to dissect the impact of immunosuppressive medication on cellular and humoral immune responses in RMD patients receiving the inactivated COVID-19 vaccine.Methods:A total of 28 RMD patients and five healthy controls(HCs)receiving two doses of the inactivated COVID-19 vaccine(Sinovac-CoronaVac)were prospectively enrolled.Blood samples were collected before the primary vaccination(Week 0)and one week after the second vaccination(Week 5).Neutralizing antibody(nAb)titers and autoantibody titers were measured by a pseudovirus-based neutralization assay and enzyme-linked immunosorbent assay,respectively.CD4^(+)T-cell and CD19^(+)B-cell subsets and serum cytokines were analyzed by flow cytometry.Results:The inactivated COVID-19 vaccine was immunogenic in RMD patients and HCs after the second vaccination,but the nAb titers were lower in RMD patients than those in HCs.Only patients with systemic lupus erythematosus(SLE)had notably increased nAb titers.Remarkably,IgG^(+)CD27^(+),IgG^(+)IgG1^(+),and IgG^(+)IgG1^(−)B cells were reduced,whereas IgG−IgG1^(+)B cells,and total IgA and IgG titers were markedly increased.However,Tfh cell and Tfr cell subsets and cytokines produced by Tfh cells were not increased.The flare rate was low in RMD patients with comparable autoantibody titers,unchanged CD4^(+)T cell subsets and serum proinflammatory cytokines(interleukin[IL]-6,IL-17,interferon-γ,and tumor necrosis factor-α)after the second vaccination.Conclusions:Immunosuppressive therapy decreased the immunogenicity of the vaccine and maintained a low flare rate by selectively modulating B cell but not CD4^(+)T cell responses in RMD patients receiving the inactivated COVID-19 vaccine.Optimization of the treatment regimen might ensure a durable and robust COVID-19 vaccination response.展开更多
In this study,Gd and Ca co-doped ceria electrolytes with the compositions of Ce_(0.8)Gd_(0.2-x)Ca_(x)O_(2-δ)(x=0-0.08) were prepared by a novel gel-casting method.The effects of the addition of Ca on the phase compos...In this study,Gd and Ca co-doped ceria electrolytes with the compositions of Ce_(0.8)Gd_(0.2-x)Ca_(x)O_(2-δ)(x=0-0.08) were prepared by a novel gel-casting method.The effects of the addition of Ca on the phase compositions,sintering behavio r,and electrical prope rties of samples were investigated.According to the scanning electron microscope results and relative density measurement results,it is found that the addition of particular quantity of CaO can promote the sintering densification with a uniform grain growth.When the sintering temperature is 1400℃,the sample with 6 mol% addition of Ca has the highest relative density,which reaches 98.5% of the theoretical density.The electrical properties testing results confirm that the electrical conductivity of the samples can be improved significantly by doping appropriate CaO content.The maximum conductivity of 0.082 S/cm can be obtained at 800℃ in the Ce_(0.8)Gd_(0.12)-Ca_(0.06)O_(1.87) sample.It suggests that CaO can be used as an effective sintering aid and a codopant on the optimization of electrical properties for ceria-based electrolytes.展开更多
基金National Natural Science Foundation of China,Grant/Award Numbers:82271784,81974251,82071816National Key Research and Development Program of China,Grant/Award Number:2017YFC0909002。
文摘Background:Immunosuppressive medication reduces the immunogenicity of the coronavirus disease 2019(COVID-19)vaccines in patients with rheumatic and musculoskeletal diseases(RMDs).However,the underlying mechanism remains unclear.The primary aim of our study was to dissect the impact of immunosuppressive medication on cellular and humoral immune responses in RMD patients receiving the inactivated COVID-19 vaccine.Methods:A total of 28 RMD patients and five healthy controls(HCs)receiving two doses of the inactivated COVID-19 vaccine(Sinovac-CoronaVac)were prospectively enrolled.Blood samples were collected before the primary vaccination(Week 0)and one week after the second vaccination(Week 5).Neutralizing antibody(nAb)titers and autoantibody titers were measured by a pseudovirus-based neutralization assay and enzyme-linked immunosorbent assay,respectively.CD4^(+)T-cell and CD19^(+)B-cell subsets and serum cytokines were analyzed by flow cytometry.Results:The inactivated COVID-19 vaccine was immunogenic in RMD patients and HCs after the second vaccination,but the nAb titers were lower in RMD patients than those in HCs.Only patients with systemic lupus erythematosus(SLE)had notably increased nAb titers.Remarkably,IgG^(+)CD27^(+),IgG^(+)IgG1^(+),and IgG^(+)IgG1^(−)B cells were reduced,whereas IgG−IgG1^(+)B cells,and total IgA and IgG titers were markedly increased.However,Tfh cell and Tfr cell subsets and cytokines produced by Tfh cells were not increased.The flare rate was low in RMD patients with comparable autoantibody titers,unchanged CD4^(+)T cell subsets and serum proinflammatory cytokines(interleukin[IL]-6,IL-17,interferon-γ,and tumor necrosis factor-α)after the second vaccination.Conclusions:Immunosuppressive therapy decreased the immunogenicity of the vaccine and maintained a low flare rate by selectively modulating B cell but not CD4^(+)T cell responses in RMD patients receiving the inactivated COVID-19 vaccine.Optimization of the treatment regimen might ensure a durable and robust COVID-19 vaccination response.
基金Project supported by the Natural Science Foundation of Anhui Province of China(1708085ME112)。
文摘In this study,Gd and Ca co-doped ceria electrolytes with the compositions of Ce_(0.8)Gd_(0.2-x)Ca_(x)O_(2-δ)(x=0-0.08) were prepared by a novel gel-casting method.The effects of the addition of Ca on the phase compositions,sintering behavio r,and electrical prope rties of samples were investigated.According to the scanning electron microscope results and relative density measurement results,it is found that the addition of particular quantity of CaO can promote the sintering densification with a uniform grain growth.When the sintering temperature is 1400℃,the sample with 6 mol% addition of Ca has the highest relative density,which reaches 98.5% of the theoretical density.The electrical properties testing results confirm that the electrical conductivity of the samples can be improved significantly by doping appropriate CaO content.The maximum conductivity of 0.082 S/cm can be obtained at 800℃ in the Ce_(0.8)Gd_(0.12)-Ca_(0.06)O_(1.87) sample.It suggests that CaO can be used as an effective sintering aid and a codopant on the optimization of electrical properties for ceria-based electrolytes.