Local Renal Autoantibody Production in Lupus Nephritis

作者：Marion Espéli, Susanne Bökers, Giovanna A. Giannico, Harriet A. Dickinson, Victoria Bardsley, Agnes B. Fogo, Kenneth G. C. Smith · 发表于：Journal of the American Society of Nephrology · 年份：2010 · DOI：10.1681/asn.2010050515 · 被引用次数：157 · 研究领域：Systemic Lupus Erythematosus Research、T-cell and B-cell Immunology、Renal Diseases and Glomerulopathies

Autoantibodies are central to the pathogenesis of several autoimmune diseases including systemic lupus erythematosus. Plasma cells secrete these autoantibodies, but the anatomical sites of these cells are not well defined. Here, we found that although dsDNA-specific plasma cells in NZB/W mice were present in spleen and bone marrow, a large number were in the kidneys and their number correlated with the serum dsDNA-IgG titer. We observed renal plasma cells only in mice with nephritis, where they located mainly to the tubulointerstitium of the cortex and outer medulla. These cells had the phenotypic characteristics of fully differentiated plasma cells and, similar to long-lived bone marrow plasma cells, they were not in cell cycle. In patients with lupus nephritis, plasma cells were often present in the medulla in those with the most severe disease, especially combined proliferative and membranous lupus nephritis. The identification of the kidney as a major site of autoreactive plasma cells has implications for our understanding of the pathogenesis of lupus nephritis and for strategies to deplete autoreactive plasma cells, a long-standing therapeutic aim.