Abstract
Bullous pemphigoid (BP) is by far the most common autoimmune blistering dermatosis that mainly occurs in the elderly. The BP180 is a transmembrane glycoprotein, which is highly immunodominant in BP. The structure and location of BP180 indicate that it is a significant autoantigen and plays a key role in blister formation. Autoantibodies from BP patients react with BP180, which leads to its degradation and this has been regarded as the central event in BP pathogenesis. The consequent blister formation involves the activation of complement-dependent or -independent signals, as well as inflammatory pathways induced by BP180/anti-BP180 autoantibody interaction. As a multi-epitope molecule, BP180 can cause dermal–epidermal separation via combining each epitope with specific immunoglobulin, which also facilitates blister formation. In addition, some inflammatory factors can directly deplete BP180, thereby leading to fragility of the dermal–epidermal junction and blister formation. This review summarizes recent investigations on the role of BP180 in BP pathogenesis to determine the potential targets for the treatment of patients with BP.
Highlights
Bullous pemphigoid (BP), by far the most common autoimmune blistering disease, is induced by autoantibodies against the structural components of the dermal–epidermal junction (DEJ) [1]
The amount of circulating eosinophils is correlated with the levels of both NC16A-specific immunoglobulin G (IgG) and IgE in BP sera [106]. These results provide indirect evidence that anti-BP180 NC16A IgE autoantibodies contribute to BP-like damage and to certain distinct clinical features by triggering mast cell degranulation and basophil histamine release that is FcεRI dependent [106, 107] (Figure 3A)
Like linear IgA bullous disease (LAD), the anti-BP180 IgA autoantibodies directly act on NC16A domain, leading to the release of inflammatory factors and neutrophils, degranulation of neutrophils and mast cells, and release of proteolytic enzymes—all of which are similar to the effects of IgG and IgE [118] (Figure 3A)
Summary
Bullous pemphigoid (BP), by far the most common autoimmune blistering disease, is induced by autoantibodies against the structural components of the dermal–epidermal junction (DEJ) [1]. Like LAD, the anti-BP180 IgA autoantibodies directly act on NC16A domain, leading to the release of inflammatory factors and neutrophils, degranulation of neutrophils and mast cells, and release of proteolytic enzymes—all of which are similar to the effects of IgG and IgE [118] (Figure 3A). The NC14A region can be genetically deleted in C57BL/6 mice, which have less amount of BP180 in skin but have normal ectodomain shedding [130] They spontaneously produce IgG and IgA autoantibodies against BP180 and present eosinophilic infiltrations, as well as the clinical features of pruritus and crusted erosions [130]. The development of novel ELISA system to detect such autoantibodies is necessary [77]
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