Mechanisms of tissue injury in lupus nephritis

Abstract

Systemic lupus erythematosus is a prototypic autoimmune disease characterized by autoantibody production and immune complex formation/deposition in target organs such as the kidney. Resultant local inflammation then leads to organ damage. Nephritis, a major cause of morbidity and mortality in patients with lupus, occurs in approximately 50% of lupus patients. In the present review, we provide an overview of the current research and knowledge concerning mechanisms of renal injury in both lupus-prone mouse models and human lupus patients.

Figure 1

Summary of proposed pathogenic mechanisms in tissue injury in lupus nephritis. Top right: The first step leading to nephritis involves the production of autoantibodies to self-antigens followed by formation of immune complexes (ICs) in glomeruli. IC deposition leads to complement activation and intrinsic renal cell activation (mesangial cells (MC) and endothelial cells (EC)), both leading to local chemokine and cytokine inflammation. Chemokine expression leads to an influx of inflammatory cells such as lymphocytes and macrophages. Left: Influx of immune cells leads to interstitial as well as further glomeruli inflammation and EC activation. Activated renal cells (MC and podocytes) and infiltrating immune cells (macrophages and dendritic cells (DCs)) produce reactive nitrogen (nitric oxide (NO)) and reactive oxygen species (ROS). The combined expression of cytokines and ROS results in further renal inflammation and fibrosis, resulting in cumulative tissue destruction both at the glomerular level (top right) and the tubular level (left). Bottom right: Lymphocyte interactions and functions such as cytokine expression and antibody production contribute to inflammation and damage in the tubules and glomeruli. BCR, B-cell receptor; FcR, Fc receptor; MCP-1, monocyte chemoattractant protein-1; STAT, signal transducers and activators of transcription; TCR, T-cell receptor.