Mechanisms of Tissue Injury in Lupus Nephritis

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. In systemic lupus erythematosus (SLE), a mechanistic gap between loss of tolerance and development of end-organ damage underlies clinical disease heterogeneity. Genetic variants associated with SLE influence disease expression through effects on immune and nonimmune cells. The clinical and pathological expression of lupus nephritis is shaped by the immune response triggered by glomerular immune complexes and by the response of the kidney to local inflammation. The response of tissue-resident immune and nonimmune cells to acute inflammatory insults determines the establishment of chronic inflammation and its progression to fibrosis.