Lupus pathogenesis: role of IgE autoantibodies

Abstract

IgE is commonly known for its role in the Th2 responses, protection against helminth parasites and pathogenesis of allergy. A recent report shows that IgE autoantibodies to dsDNA plays a major role in the pathogenesis of lupus nephritis by exacerbating the interferon-α responses in plasmacytoid dendritic cells.

Figure 1

Pathogenic role of IgE autoantibodies to dsDNA in systemic lupus erythematosus. IgE autoantibodies to dsDNA form immune complexes (dsDNA-IgE IC) and bind to FcɛRI on plasmacytoid dendritic cells (pDCs). Subsequent delivery of dsDNA-IgE ICs to phago-lysosome leads to TLR9 sensing, nuclear translocation of IRF7 and NF-κB, activation of pDCs, and IFN-α, IL-6, IL-8 and TNF cytokine production. The activated pDCs promote B cell proliferation, plasma cell differentiation and immunoglobulin production via IFN-α and IL-6.