A recombinant TACI-Fc fusion protein targets IgA plasma cells in a mouse model of systemic lupus erythematosus

To investigate molecular profiles during the progression of LN, we carried out gene expression analysis on kidneys and spleens from lupus-prone NZM2328 mice treated for four weeks from the time of disease onset.

We focused on female mice treated with BAFF and BAFF/APRIL inhibitors alongside cyclophosphamide as a standard therapy to identify mechanisms associated with improved renal outcomes. Inhibition of BAFF alone had a limited impact on gene expression profiles of diseased mice, decreasing myeloid cell and increasing metabolic gene signatures. However, targeting both BAFF and APRIL through competitive inhibition with a TACI-Fc fusion protein significantly altered immune populations in the spleen and depleted IgA plasma cells and also decreased pro-inflammatory immune cells and cytokines in the kidneys of diseased mice.