Figure 1: Contribution of autoreactive IgE to SLE pathophysiology
In SLE, plasmacytoid dendritic cells (pDC) and basophils (BAS) are recruited to secondary lymphoid organs. There, pDC and BAS contribute to the pathogenesis of SLE by promoting AAb production through the production of type I interferon (IFNα/β) and IL-4, respectively. IgG AAb, through Fcγ receptors, and IgE AAb, through FcεRI, cooperate to facilitate the addressing of dsDNA to TLR9 in endosomal compartments of pDC leading to increased type I IFN production. IFNα and β promote IFN-responsive gene transcription and directly act on B cells to facilitate maturation and differentiation into antibody-secreting cells (plasma cells). On basophils, autoreactive IgG may engage the inhibitory receptor for IgG, FcγRIIB, along with FcεRI engagement through autoreactive IgE. The integrated signal leads to cytokine (IL-4) production without inducing degranulation.