New Insights Into the Pathogenesis of Bullous Pemphigoid: 2019 Update

Giovanni Genovese, Giovanni Di Zenzo, Emanuele Cozzani, Emilio Berti, Massimo Cugno, Angelo Valerio Marzano, Giovanni Genovese, Giovanni Di Zenzo, Emanuele Cozzani, Emilio Berti, Massimo Cugno, Angelo Valerio Marzano

Abstract

There are several lines of evidence indicating that the physiopathological bases of bullous pemphigoid (BP), the most common subepidermal autoimmune bullous disease, are hallmarked by the production of autoantibodies directed against the hemidesmosomal anchoring proteins BP180 and BP230. In contrast to the robustness of the latter assumption, the multifaceted complexity of upstream and downstream mechanisms implied in the pathogenesis of BP remains an area of intense speculation. So far, an imbalance between T regulatory cells and autoreactive T helper (Th) cells has been regarded as the main pathogenic factor triggering the autoimmune response in BP patients. However, the contributory role of signaling pathways fostering the B cell stimulation, such as Toll-like receptor activation, as well as that of ancillary inflammatory mechanisms responsible for blister formation, such as Th17 axis stimulation and the activation of the coagulation cascade, are still a matter of debate. In the same way, the pathomechanisms implied in the loss of dermal-epidermal adhesion secondary to autoantibodies binding are not fully understood. Herein, we review in detail the current concepts and controversies on the complex pathogenesis of BP, shedding light on the most recent theories emerging from the literature.

Keywords: autoantibodies; autoimmune blistering diseases; autoimmunity; bullous pemphigoid; pathogenesis; skin.

Figures

Figure 1
Figure 1
Representative figure of the main pathogenic pathways implied in blister formation in patients with bullous pemphigoid.

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