Figure 2.

IgE- and eosinophil-mediated complement-independent pathways in bullous pemphigoid. (A) BP180 IgE autoantibodies and BP180-IgE complexes bind to the cutaneous basement membrane and the FcϵR1 on eosinophils as well as mast cells and basophils. This results in release of proteases (e.g. MMP9), eosinophil granule proteins (ECP, EDN), eosinophil extracellular traps, as well as reactive nitric oxide-derived oxidants (NOS). (B) Keratinocytes release IL-5, RANTES, and eotaxin-1 as a response to eosinophil granule proteins. (C) this positive feedback loop results in an increase in tissue eosinophilia and eosinophilic spongiosis. Inhibitory therapeutic antibodies are shown in boxes with red arrows leading to their downstream target.