Braunstein Marsela
, Waterloo, ON, Canada.
BMC Nephrol. 2025 Sep 1;26(1):507. doi: 10.1186/s12882-025-04434-3.
Lupus nephritis (LN), a serious complication of systemic lupus erythematosus (SLE), involves complex immune dysregulation that leads to chronic renal inflammation and progressive tissue damage. Despite decades of use of standard immunosuppressive therapy, treatment responses remain variable, and many patients experience relapses or develop end-stage renal disease. This review synthesizes emerging insights into the immunopathogenesis of LN, drawing on studies from single-cell transcriptomics, signaling pathway analyses and renal tissue immunology. It examines the role of both innate and adaptive immune cells in mediating disease. The therapeutic landscape is rapidly evolving with novel biologics targeting B cell survival and cytokine signaling, small-molecule inhibitors modulating intracellular pathways, and promising developments in cell-based interventions. Notably, recent clinical case series have demonstrated that CD19-directed chimeric antigen receptor (CAR) T-cell therapy can induce durable drug-free remission in LN, representing a transformative approach to immune modulation. These advances are further supported by the application of multi-omics platforms to refine biomarker-driven disease monitoring and personalized treatment. Integrating immunologic and technological innovations holds the potential to redefine therapeutic strategies in LN. Precision medicine approaches that leverage targeted therapies, immune resetting modalities, and biomarker-guided clinical decisions may significantly improve long-term renal outcomes and patient quality of life.
狼疮性肾炎（LN）是系统性红斑狼疮（SLE）的一种严重并发症，涉及复杂的免疫失调，可导致慢性肾脏炎症和进行性组织损伤。尽管标准免疫抑制疗法已使用数十年，但治疗反应仍存在差异，许多患者会复发或发展为终末期肾病。本综述综合了单细胞转录组学、信号通路分析和肾组织免疫学等研究中对LN免疫发病机制的新见解。它探讨了固有免疫细胞和适应性免疫细胞在介导疾病中的作用。随着针对B细胞存活和细胞因子信号传导的新型生物制剂、调节细胞内途径的小分子抑制剂以及基于细胞的干预措施的有前景的发展，治疗格局正在迅速演变。值得注意的是，最近的临床病例系列表明，靶向CD19的嵌合抗原受体（CAR）T细胞疗法可诱导LN患者实现持久的无药缓解，这代表了一种变革性的免疫调节方法。多组学平台的应用进一步支持了这些进展，以优化生物标志物驱动的疾病监测和个性化治疗。整合免疫学和技术创新有可能重新定义LN的治疗策略。利用靶向治疗、免疫重置模式和生物标志物指导的临床决策的精准医学方法可能会显著改善长期肾脏结局和患者生活质量。
