The Role of Eosinophils in Bullous Pemphigoid: A Developing Model of Eosinophil Pathogenicity in Mucocutaneous Disease

Abstract

Bullous pemphigoid (BP) is an autoimmune blistering disease which carries a significant mortality and morbidity. While historically BP has been characterized as an IgG driven disease mediated by anti-BP180 and BP230 IgG autoantibodies, developments in recent years have further elucidated the role of eosinophils and IgE autoantibodies. In fact, eosinophil infiltration and eosinophilic spongiosis are prominent features in BP. Several observations support a pathogenic role of eosinophils in BP: IL-5, eotaxin, and eosinophil-colony stimulating factor are present in blister fluid; eosinophils line the dermo-epidermal junction (DEJ) in the presence of BP serum, metalloprotease-9 is released by eosinophils at the site of blisters; eosinophil degranulation proteins are found on the affected basement membrane zone as well as in serum corresponding with clinical disease; eosinophil extracellular DNA traps directed against the basement membrane zone are present, IL-5 activated eosinophils cause separation of the DEJ in the presence of BP serum; and eosinophils are the necessary cell required to drive anti-BP180 IgE mediated skin blistering. Still, it is likely that eosinophils contribute to the pathogenesis of BP in numerous other ways that have yet to be explored based on the known biology of eosinophils. We herein will review the role of eosinophils in BP and provide a framework for understanding eosinophil pathogenic mechanisms in mucocutaneous disease.

Mechanisms of pathogenic effects of eosinophil cationic protein and eosinophil‐derived neurotoxin on human keratinocytes

“…IL‐5, eotaxin‐1 and RANTES are known to have a significant role in BP . Upregulation of eotaxin‐1 and RANTES is associated with eosinophil activation in BP .…”

“…Skin eosinophilia can be seen in several dermatoses including bullous pemphigoid (BP), where a cutaneous deposition of eosinophil degranulation proteins is a major feature . Eosinophil degranulation proteins include major basic protein (MBP), eosinophil peroxidase (EPO), CLC/Gal‐10 and the two ribonucleases (RNAses): eosinophil cationic protein (ECP) and eosinophil‐derived neurotoxin (EDN) …”

The Role of Collagen XVII in Cancer: Squamous Cell Carcinoma and Beyond

“…The binding of autoantibodies with the ectodomain (ex. NC16A) can lead to the development of bullous pemphigoid, resulting in skin blistering and dermatitiss (20,38,39).…”

Exosomes in chronic inflammatory skin diseases and skin tumors

“…Bullous pemphigoid is an autoimmune blistering disease characterized by autoantibodies against the hemidesmosomal proteins, BP180 and BP230, which are deposited in the epithelial basement membrane zone . The histological presentation of BP may vary with clinical presentation, but typical histopathological findings are subepidermal blisters with inflammatory cell infiltrates of variable intensity, composed of lymphocytes, neutrophils, and characteristically, eosinophils . Fang and colleagues have found that CD63, CD81 and CD9 are marker proteins in exosomes purified from the blister fluids of BP patients.…”