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. 2019 May 3;10:978. doi: 10.3389/fimmu.2019.00978

Figure 1.

Figure 1

Schematic representation of the pathophysiology and new therapeutic targets of pemphigus and pemphigoid diseases. The pathophysiology of pemphigus and pemphigoid diseases consists of the following three phases: (1) CD4+T cells promote autoreactive B cell activation, proliferation, and differentiation to plasma cells that produce pathogenic autoantibodies. (2) Circulating pathogenic antibodies are transferred to the dermal epidermal junction or intracellular space of the epidermis. Neonatal Fc receptor (FcRn) plays a role in prolonging the half-life of IgG antibodies during this phase. (3) After the binding of pathogenic autoantibodies to target molecules, pro-inflammatory cells such as granulocytes and macrophages are recruited to the immune complex in lesional skin by chemokines (e.g., eotaxin). Then, granulocytes elicit reactive oxygen species (ROS), elastases, and proteases, resulting in tissue damage such as blisters and/or erythema, which are clinical symptoms in pemphigoid diseases but not in pemphigus diseases. Cytokines [e.g., interleukin (IL)-1beta and IL-18] and Th17 polarization are thought to enhance local inflammation. During the antibody production phase, rituximab and ofatumumab deplete autoreactive B cells to prevent their differentiation to plasma cells. PolyTregs act on CD4+ T cells, and VAY736 and PRN1008 act on autoreactive B cells, resulting in less activation of autoreactive B cells. In the transcytosis phase, intravenous immunoglobulin (IVIg), SYNT001, and ARGX-113 saturate FcRn, contributing to the shortened half-life of pathogenic autoantibodies. In the effector phase, ixekizumab restores Th17 polarization and suppresses inflammatory augmentation. AC-203 modulates cytokines such as IL-1beta and IL-18, contributing to decreased inflammation. The inhibition of eotaxin with bertilimumab ameliorates the recruitment of eosinophils to local inflammation sites in pemphigoid disease, especially bullous pemphigoid. Platelet-rich plasma (PRP) is thought to promote wound healing in erosions.