title: Mechanisms of Kidney Injury in Lupus Nephritis - the Role of Anti-dsDNA Antibodies.
abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a breakdown of self-tolerance, production of auto-antibodies and immune-mediated injury, resulting in damage accrual in multiple organs. Kidney involvement, termed lupus nephritis, is a major cause of morbidity and mortality that affects over half of the SLE population during the course of disease. The etiology of lupus nephritis is multifactorial and remains to be fully elucidated. Accumulating evidence suggests that in addition to forming immune complexes and triggering complement activation, anti-dsDNA antibodies contribute to the pathogenesis of lupus nephritis through binding, either directly or indirectly, to cross-reactive antigens or chromatin materials, respectively, to resident renal cells and/or extracellular matrix components, thereby triggering downstream cellular activation and proliferation as well as inflammatory and fibrotic processes. Several cross-reactive antigens that mediate anti-dsDNA antibody binding have been identified, such as annexin II and alpha-actinin. This review discusses the mechanisms through which anti-dsDNA antibodies contribute to immunopathogenesis in lupus nephritis. Corticosteroids combined with either mycophenolic acid (MPA) or cyclophosphamide is the current standard of care immunosuppressive therapy for severe lupus nephritis. This review also discusses recent data showing distinct effects of MPA and cyclophosphamide on inflammatory and fibrotic processes in resident renal cells.
authors.affiliation: Department of Medicine, Queen Mary Hospital, University of Hong Kong , Hong Kong , China.
authors.forename: Susan
authors.initials: S
authors.lastname: Yung
authors.affiliation: Department of Medicine, Queen Mary Hospital, University of Hong Kong , Hong Kong , China.
authors.forename: Tak Mao
authors.initials: TM
authors.lastname: Chan
keywords: anti-dsDNA antibodies; cyclophosphamide; fibrosis; inflammation; lupus nephritis; mesangial cells; mycophenolic acid; proximal renal tubular epithelial cells