Pathogenic cellular and molecular mediators in lupus nephritis

Abstract

Kidney involvement in patients with systemic lupus erythematosus — lupus nephritis (LN) — is one of the most important and common clinical manifestations of this disease and occurs in 40–60% of patients. Current treatment regimens achieve a complete kidney response in only a minority of affected individuals, and 10–15% of patients with LN develop kidney failure, with its attendant morbidity and considerable prognostic implications. Moreover, the medications most often used to treat LN — corticosteroids in combination with immunosuppressive or cytotoxic drugs — are associated with substantial side effects. Advances in proteomics, flow cytometry and RNA sequencing have led to important new insights into immune cells, molecules and mechanistic pathways that are instrumental in the pathogenesis of LN. These insights, together with a renewed focus on the study of human LN kidney tissue, suggest new therapeutic targets that are already being tested in lupus animal models and early-phase clinical trials and, as such, are hoped to eventually lead to meaningful improvements in the care of patients with systemic lupus erythematosus-associated kidney disease. This Review examines the contribution of innate and adaptive immune cells to the pathogenesis of lupus nephritis, including new insights into the molecular mechanisms that drive this disease, such as recognition of endogenous chromatin by endosomal and cytosolic nucleic acid sensors.