Bullous pemphigoid induced by pembrolizumab in a patient with advanced melanoma expressing collagen XVII

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease characterized by deposition of autoantibodies at the basement membrane zone. In an experimental BP model in mice, the subepidermal blistering is mediated by antibodies directed against the hemidesmosomal protein BP180 (collagen XVII, BPAG2), and depends on complement activation and neutrophil infiltration. Gelatinase B is present in BP blister fluid and can cleave BP180. In this study we investigated the role of gelatinase B in the immunopathogenesis of experimental BP using mice containing targeted disruption of the gelatinase B (MMP-9, 92 kD gelatinase) gene. Gelatinase B–deficient mice were resistant to the blistering effect of intracutaneous anti-mBP180 antibodies, although these mice showed deposition of autoantibodies at the basement membrane zone and neutrophil recruitment to the skin comparable to that observed in the control mice. Interleukin 8 given intradermally concomitantly with pathogenic anti-mBP180 elicited a significant neutrophil recruitment into the skin in gelatinase B–deficient mice, but blistering did not occur. However, gelatinase B–deficient mice reconstituted with neutrophils from normal mice developed blistering in response to anti-mBP180 antibodies. These results implicate neutrophil-derived gelatinase B in the pathogenesis of experimental BP and might lead to novel therapeutic strategies for BP.

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Epitope-Dependent Pathogenicity of Antibodies Targeting a Major Bullous Pemphigoid Autoantigen Collagen XVII/BP180

Journal of Investigative Dermatology ◽

10.1016/j.jid.2015.11.030 ◽

2016 ◽

Vol 136 (5) ◽

pp. 938-946 ◽

Cited By ~ 22

Author(s):

Mayumi Wada ◽

Wataru Nishie ◽

Hideyuki Ujiie ◽

Kentaro Izumi ◽

Hiroaki Iwata ◽

...

Keyword(s):

Bullous Pemphigoid ◽

Collagen Xvii

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Update on the pathogenesis of bullous pemphigoid: An autoantibody-mediated blistering disease targeting collagen XVII

Journal of Dermatological Science ◽

10.1016/j.jdermsci.2013.12.001 ◽

2014 ◽

Vol 73 (3) ◽

pp. 179-186 ◽

Cited By ~ 62

Author(s):

Wataru Nishie

Keyword(s):

Bullous Pemphigoid ◽

Collagen Xvii ◽

Blistering Disease

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Pemphigus and Bullous Pemphigoid

10.2310/fm.1122 ◽

2020 ◽

Author(s):

Aakaash Varma ◽

Annette Czernik ◽

Jacob Levitt

Keyword(s):

Botulinum Toxin ◽

Bullous Pemphigoid ◽

Clinical Features ◽

Indirect Immunofluorescence ◽

Direct Immunofluorescence ◽

Topical Steroids ◽

Bladder Epithelium ◽

Paraneoplastic Pemphigus ◽

Rat Bladder ◽

Collagen Xvii

Pemphigus disorders are characterized by acantholysis, whereas pemphigoid disorders are characterized by a dermal-epidermal split. Diagnosis of pemphigus or pemphigoid relies on a combination of positive anti-desmoglein or anti-collagen XVII serology, confirmatory direct immunofluorescence, and clinical features. Treatment for immunobullous disease revolves around various immunosuppressants, most often some combination of rituximab, prednisone, and IVIg. Paraneoplastic pemphigus is characterized by hemorrhagic crusting of the lips with positive indirect immunofluorescence on rat bladder epithelium, which should prompt a search for malignancy. Hailey-Hailey disease is a genetically mediated pemphigus that typically occurs in skin folds and responds to a number of agents including botulinum toxin, topical steroids, and other anecdotal therapies. This review contains 17 figures, 2 tables, and 109 references. Keywords: blister, pemphigus, bullous, rituximab, bullae, prednisone

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