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.

Platelet-rich plasma vs bone marrow aspirate concentrate:An overview of mechanisms of action and orthobiologic synergistic effects

The use of orthobiologics as a novel therapy for the treatment of numerous musculoskeletal disorders has increased considerably over the past decade.Currently,there are multiple alternatives available as suitable treatments;however,the use of autologous blood-derived products such as platelet-rich plasma(PRP),bone marrow aspirate(BMA)and BMA concentrate(BMAC),specifically,is expanding.Although many investigations attempted to demonstrate the effectiveness of these therapies,even with positive results,the literature lacks standardized protocols and overall accuracy in study designs,which leads to variance and difficulty in reproducibility of protocols.The efficacy of PRP for the treatment of cartilage,bone and muscle tissues is well known.Although BMAC has generated optimistic results for the same purposes,its applicability in clinical trials is still relatively recent when compared to PRP.Both products demonstrate the potential to set forth reparative processes,each in their own distinct mechanism.The combination of these biological products has been previously proposed,yet little is known about their synergism.Evidence indicates that growth factor,cytokine,and chemokine profiles seen in both PRP and BMAC vary but are likely to work synergistically to enhance musculoskeletal healing.BMAC products seem to work well without PRP;however,the addition of PRP to BMAC has been shown to act as a rich and natural source of culture medium for stem cells located either peripherally or in the bone marrow itself.Nevertheless,additional variables associated with the use of BMAC and PRP in orthopedics must be further evaluated in order to consolidate the efficacy of this therapeutic strategy.