Immunosuppressant-refractory Multifaceted Immune Dysregulations for Systemic Lupus Erythematosus.

Abstract

While the systemic lupus erythematosus (SLE), a severe autoimmune disease, is known to relapse frequently after treatment, none of the previous single-cell studies have examined the immune dynamics and their potential contribution to this relapse in the real clinical setting. To address this issue, here we employed single-cell multi-omics profiling to delineate immune repertoire dynamics during the immunosuppressant-based standard of care. Further analysis showed that the canonical therapy fails to restore various critical abnormalities, including the drop in mutational load of B and plasma cells, and the clonal expansion of CD4+ Th1 and CD8+ memory T cells. We also integrated our data with published SLE datasets to compile a comprehensive SLE immune atlas of about 1.6 million cells. Our study provides valuable data and sheds light on the underlying multifaceted unresolved dysregulation upon SLE immunosuppressant therapy under the real clinical setting; such dysregulation may further contribute to the high post-treatment relapse rate and thus call for additional target-specific treatment strategies.