单细胞多组学揭示系统性红斑狼疮免疫抑制治疗后仍存在的多维免疫失调
Immunosuppressant-refractory Multifaceted Immune Dysregulations for Systemic Lupus Erythematosus
研究用单细胞多组学在真实临床场景下追踪系统性红斑狼疮（SLE）患者接受免疫抑制剂标准治疗期间的免疫组库动态，发现该疗法未能纠正 B 细胞和浆细胞的突变负荷下降，也未能阻止 CD4+ Th1 与 CD8+ 记忆 T 细胞的克隆扩增。作者还将自有数据与已发表的 SLE 数据集整合，构建了约 160 万细胞的 SLE 免疫图谱，并指出这些持续存在的失调可能与该病治疗后高复发率相关。
来源：Genomics, Proteomics & Bioinformatics · doi.org
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.