Local renal autoantibody production in lupus nephritis.

Espeli M, Bökers S, Giannico G, Dickinson HA, Bardsley V, Fogo AB, Smith KG
J Am Soc Nephrol. 2011 22 (2): 296-305

PMID: 21088295 · PMCID: PMC3029902 · DOI:10.1681/ASN.2010050515

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.

MeSH Terms (18)

Animals Antibodies, Antinuclear Autoantibodies Basement Membrane Biopsy Chemokine CXCL12 Female Humans Ki-67 Antigen Kidney Leukosialin Lupus Erythematosus, Systemic Lupus Nephritis Male Mice Mice, Inbred C57BL Mice, Inbred NZB Plasma Cells

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