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SCIENTIFIC PUBLICATIONS BY ALR FUNDED RESEARCHERS

Selective blockade of BAFF prevents and treats SLE nephritis in NZM2410 mice - Dr. Anne Davidson

November 10, 2009

Objectives: To determine whether BAFF or combined BAFF/APRIL blockade is effective in a mouse model of SLE nephritis characterized by rapidly progressive glomerulosclerosis.

Methods: NZM2410 mice at early and late stages of disease were treated with a short course of BAFF-R-Ig or TACI-Ig. Mice were followed for proteinuria and serologic profile every two weeks. Immunohistochemical, flow cytometric and ELISpot analyses of spleens, kidneys and bone marrows was performed after 8 weeks and after 33 weeks.

Results: A short course of selective blockade of BAFF alone was sufficient to prevent and treat SLE nephritis in NZM2410 mice despite the formation of pathogenic autoantibodies. Decreases in spleen size and B cell depletion persisted for more than 33 weeks after treatment and resulted in secondary decreases in CD4 memory T cell formation and activation of splenic and peripheral monocytes. Immune complex deposition in the kidneys was dissociated from renal damage and from activation of renal endothelial and resident dendritic cells.

Conclusions: Selective blockade of BAFF alone resulting in B cell depletion and splenic collapse was sufficient to prevent and treat disease in this model of non-inflammatory SLE nephritis. This shows that the inflammatory microenvironment may be a determinant of the outcome of B cell modulation strategies.

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Source: Alliance for Lupus Research
Funded Research


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