PURPOSE OF REVIEW: Traditionally, lupus nephritis has been considered an autoimmune disorder of unknown origin and a complex pathophysiology, but in recent years, its pathogenesis has been unraveled. RECENT FINDINGS: In individuals with unfortunate combinations of gene variants, environmental triggers such as certain drugs or viral infections allow autoimmunization against nuclear antigens, as evident by the presence of antinuclear antibodies. The expansion of autoreactive lymphocyte clones is driven by the nucleic acid component of nuclear particles from netting neutrophils and other dying cells as these activate immunity via viral nucleic acid-specific Toll-like receptors in dendritic cells and B cells. This process triggers interferon-α signaling-related antiviral immunity; hence, lupus symptoms are often indistinguishable from those of viral infections. Inside the kidney, lupus autoantibodies bind several autoantigens and trigger injury and inflammation, either in the mesangium (classes I/II), or along both sides of the glomerular basement membrane (classes III/IV/V). In addition, vascular and tubulointerstitial inflammation contribute to the immunopathology of lupus nephritis. SUMMARY: Eventually, a better understanding of lupus nephritis pathogenesis will allow the identification of therapeutic targets that will prove effective not only in animal models but also in randomized clinical trials.
PURPOSE OF REVIEW: Traditionally, lupus nephritis has been considered an autoimmune disorder of unknown origin and a complex pathophysiology, but in recent years, its pathogenesis has been unraveled. RECENT FINDINGS: In individuals with unfortunate combinations of gene variants, environmental triggers such as certain drugs or viral infections allow autoimmunization against nuclear antigens, as evident by the presence of antinuclear antibodies. The expansion of autoreactive lymphocyte clones is driven by the nucleic acid component of nuclear particles from netting neutrophils and other dying cells as these activate immunity via viral nucleic acid-specific Toll-like receptors in dendritic cells and B cells. This process triggers interferon-α signaling-related antiviral immunity; hence, lupus symptoms are often indistinguishable from those of viral infections. Inside the kidney, lupus autoantibodies bind several autoantigens and trigger injury and inflammation, either in the mesangium (classes I/II), or along both sides of the glomerular basement membrane (classes III/IV/V). In addition, vascular and tubulointerstitial inflammation contribute to the immunopathology of lupus nephritis. SUMMARY: Eventually, a better understanding of lupus nephritis pathogenesis will allow the identification of therapeutic targets that will prove effective not only in animal models but also in randomized clinical trials.