GSE163014
Single-cell RNA sequencing of Tocilizumab-treated peripheral blood mononuclear cells as an in vitro model of inflammation
COVID-19 has posed a significant threat to global health. Early data has revealed that IL-6, a key regulatory cytokine, plays an  important role in the cytokine storm of COVID-19. Multiple trials are therefore looking at the effects of Tocilizumab, an IL-6  receptor antibody that inhibits IL-6 activity, on treatment of COVID-19, with promising findings. As part of a clinical trial looking  at the effects of Tocilizumab treatment on kidney transplant recipients with subclinical rejection, we performed single-cell RNA  sequencing of comparing stimulated PBMCs before and after Tocilizumab treatment. We leveraged this data to create an in vitro  cytokine storm model, to better understand the effects of Tocilizumab in the presence of inflammation. Tocilizumab-treated cells  had reduced expression of inflammatory-mediated genes and biologic pathways, particularly amongst monocytes. These results  support the hypothesis that Tocilizumab may hinder the cytokine storm of COVID-19, through a demonstration of biologic impact at  the single-cell level. Overall design: Examination of peripheral blood mononuclear cells (PBMCs) from 15 human kidney transplant recipients, diagnosed with subclinical rejection on their 6-month post-transplant protocol biopsy and randomized to either continue standard of care (Tacrolimus, mycophenolate, and steroid) immunosuppression (control arm, 8 patients) or standard of care plus Tocilizumab (Tocilizumab treatment arm, 7 patients).