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SCIENTIFIC PUBLICATIONS BY ALR FUNDED RESEARCHERS

Activated Renal Macrophages Are Markers of Disease Onset and Disease Remission in Lupus Nephritis - Dr. Anne Davidson

November 16, 2007

Systemic lupus erythematosus (SLE)  nephritis is characterized by immune complex-mediated glomerular and tubulointerstitial inflammation, leading to chronic renal insufficiency in up to 30% of affected patients. Maintenance of disease remission after treatment of a renal flare remains a challenging clinical problem (1). Recently. it has become possible to study the mechanisms involved in induction of complete remission of nephritis in NZB/W mice. The combination of a single dose of cyclophosphamide administered along with six doses of CTLA4Ig and six doses of anti- CD154 (triple therapy) induces prompt reversal of proteinuria in NZB/W mice with established nephritis (2). Although immune complexes and complement persist in the glomeruli, histologic changes in the glomeruli reverse and there is a decrease in expression of several chemokines with efflux or death of renal inflammatory cells (2).

To further understand how inflammatory cells migrate to and from the inflamed NZB/W kidney during active disease and remission, we undertook targeted real-time PCR analysis of 61 inflammatory molecules in the kidneys of NZB/W F1 at various disease stages. Our results show that expression of inflammatory mediators follows the deposition of immune complexes in the glomeruli but that distinct subsets of genes are up-regulated at sequential stages of disease. Our findings yield insight into the progressive inflammatory process in SLE nephritis and identify an activated type II macrophage population as a key marker of proteinuria onset and disease remission.

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Source: Alliance for Lupus Research
Funded Research


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