Amelioration of Lupus Nephritis in MRL/lpr mice by Adoptive Transfer of IgM Anti-dsDNA antibodies (50.28)

Abstract

Abstract The role of IgM autoantibodies in lupus nephritis (LN) remains controversial. Our previous work with AID-deficient MRL/lpr mice demonstrated that IgM autoantibodies do not contribute to LN. In fact, these mice experienced an abrogation of LN in spite of extremely high levels of IgM autoantibodies, and their survival levels exceeded those of mice with B cells but lacking antibodies. This suggests that IgM autoantibodies may play a protective role in LN. To determine if IgM autoantibodies do in fact protect against LN and to delineate the characteristics of protective autoantibodies, MRL/lpr mice were passively transferred with serum, IgM anti-dsDNA antibodies and IgM non-autoantibodies collected/generated from AID-sufficient and -deficient MRL/lpr mice. MRL/lpr mice treated with the serum from AID-deficient MRL/lpr mice (having higher levels of IgM autoantibodies but no IgG) showed an apparent reduction in the severity of kidney disease, while the mice treated with the serum from AID-sufficient MRL/lpr mice (having both IgM and IgG autoantibodies) seemed to have increased renal impairment. MRL/lpr mice treated with Anti-dsDNA monoclonal IgM either from AID-sufficient or -deficient MRL/lpr mice displayed a reduction in the severity of kidney damage with a delayed onset of proteinuria, significantly less deposition of immune complexes, inflammatory infiltration, and apoptotic cells in the kidneys. In contrast, MRL/lpr mice treated with non-autoreactive monoclonal IgM did not seem to delay the onset of nephritis. Therefore, passive transfer of autoreactive IgM ameliorated renal impairment in MRL/lpr mice, demonstrating a protective role of IgM autoantibodies in the pathogenesis of LN. * Zhao and Jiang contributed equally to this work