Recent Developments in the Pathogenesis of Lupus Nephritis

Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease with a high incidence of renal involvement during its course contributing to disease morbidity and mortality. All compartments of the kidney may be affected by the disease but the term “lupus nephritis” is used to define glomerular pathology. There have been intensive studies to uncover the mechanisms underlying renal injury. Typically in SLE there are autoreactive B cells producing multiple autoantibodies that react with self antigens, and glomerular immune complexes are believed to be the primary mediators of renal disease. Cellular injury development at sites of immune complex deposition in the glomeruli is facilitated by both Fc receptor-mediated inflammation and direct cytotoxicity of the complement system. Deficiency of early classical complement pathway proteins that lead to defective clearance of apoptotic antigens is also linked to the etiopathogenesis. Among the various autoantibodies, the double-stranded antiDNA (dsDNA) antibody subpopulation is considered to be nephritogenic. Recent studies have revealed that chromatin fragments are the key elements in the pathogenesis as extracellular dsDNA is found in the form of nucleosome in chromatin fragments. Non-immune pathogenetic mechanisms are also considered. Although there has been a significant progress in lupus nephritis management, advances in pathogenesis is still merging.