Disease heterogeneity remains a major challenge for the understanding of systemic lupus erythematosus (SLE). Recent work has revealed the important role of nonimmune factors in the development of end-organ damage involvement, shifting the current paradigm that views SLE as a disease inflicted by a disturbed immune system on passive target organs. Here, we discuss the pathogenesis of lupus nephritis in a comprehensive manner, by incorporating the role that target organs play by withstanding and modulating the local inflammatory response. Moreover, we consider the effects that genetic variants exert on immune and nonimmune cells in order to shape the phenotype of the disease in each affected individual.

疾病异质性仍然是理解系统性红斑狼疮（SLE）的主要挑战。最近的工作揭示了非免疫因素在参与终末器官损害的发展中的重要作用，改变了当前的模式，即将SLE视为由被动目标器官上免疫系统紊乱造成的疾病。在这里，我们通过结合靶器官通过承受和调节局部炎症反应发挥的作用，以综合的方式讨论狼疮性肾炎的发病机理。此外，我们考虑了遗传变异对免疫细胞和非免疫细胞的作用，以影响每个受影响个体的疾病表型。