Blockade of the CD30/CD30L pathway inhibits renal disease in young, SLE-prone NZB/W F1 mice (50.41)

Abstract CD30 and CD30L are interacting members of the TNFR and TNF family, respectively. CD30 is expressed by subsets of activated T and B cells, whereas CD30L is expressed by subsets of activated T cells, macrophages and dendritic cells. The CD30 / CD30L interaction modulates T cell activation, germinal center formation and antibody isotype class switching. Given the importance of this pathway to B cell function, we tested the hypothesis that blockade of the CD30 / CD30L pathway would decrease or abrogate autoantibody formation and renal disease in the NZB/W F1 murine model of systemic lupus erythematosis (SLE). Young (5 mo) NZB/W F1 mice were treated with 300 μg CD30L blocking (M15-N297A) or blocking / depleting (M15-IgG2a) antibody weekly for 3 months during the onset of autoimmunity. Both treatments a) reduced the onset and severity of proteinuria, b) significantly decreased the severity of renal histologic scores, c) decreased glomerular immune complex and complement deposition and d) these effects were associated with reduced production of anti-DNA antibodies of the IgG, but not IgM isotype. CD30 / CD30L blockade may be a viable approach for the treatment of SLE.