Recent advances in the pathogenesis of lupus nephritis: autoantibodies and B cells.
Although many factors contribute to the clinical presentation and subsequent course of individuals with lupus nephritis, the formation of glomerular immune deposits is typically one of the initial events. In general, breakdown in immunologic tolerance leads to the production of autoreactive B and T cells that, either through direct infiltration and/or their secretory products, initiate inflammation. Immune deposition within glomeruli results in complement activation and recruitment of inflammatory cells, along with activation of endogenous renal cells. This inflammatory cascade leads to secretion of cytokines and chemokines, which in turn attract more infiltrating cells. Up-regulation of lymphoid-derived chemokines further enhance the cellular influx, augmenting inflammation and resulting in further tissue damage. The degree of inflammation is determined by the extent of this invasion along with both the systemic and local responses to the assault. This review focuses mainly on the contributions of pathogenic autoantibodies, autoreactive B cells to lupus nephritis, and potential immunologic therapies for lupus nephritis. Manipulation of both the cells and soluble mediators that initiate and perpetuate the disease are essential to suppressing autoreactivity and inflammation and preventing disease progression.
Su
Wanfang
W
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6144, USA.
Madaio
Michael P
MP
D000818:Animals; D001323:Autoantibodies / Q000032:analysis*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008181:Lupus Nephritis / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology*; D008211:Lymphocyte Cooperation / Q000276:immunology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D011379:Prognosis; D012307:Risk Factors; D012680:Sensitivity and Specificity
D001323:Autoantibodies; D007166:Immunosuppressive Agents