Immunosuppressive therapy selectively modulates B-cell responses in patients with rheumatic and musculoskeletal diseases receiving the inactivated COVID-19 vaccine

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.