Local Renal Autoantibody Production in Lupus Nephritis
Local Renal Autoantibody Production in Lupus Nephritis
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DOI：
10.1681/asn.2010050515
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发表时间：
2011-02-01
影响因子：
13.6
通讯作者：
Smith, Kenneth G. C.
中科院分区：
文献类型：
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作者：
Espeli, Marion;Boekers, Susanne;Smith, Kenneth G. C.
自身抗体是包括系统性红斑狼疮在内的几种自身免疫性疾病的发病机制的核心。浆细胞分泌这些自身抗体，但这些细胞的解剖部位并不明确。在这里，我们发现，虽然在NZB/W小鼠的dsDNA特异性浆细胞存在于脾脏和骨髓中，大量的是在肾脏和它们的数量与血清dsDNA-IgG滴度。我们仅在肾炎小鼠中观察到肾浆细胞，它们主要位于皮质和外髓质的肾小管上皮细胞。这些细胞具有完全分化的浆细胞的表型特征，并且类似于长寿命的骨髓浆细胞，它们不在细胞周期中。在狼疮性肾炎患者中，浆细胞通常存在于那些病情最严重的髓质中，特别是合并增殖性和膜性狼疮性肾炎。肾脏作为自身反应性浆细胞的主要部位的鉴定对于我们理解狼疮肾炎的发病机制和耗尽自身反应性浆细胞的策略（这是一个长期的治疗目标）具有意义。
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.