Autoimmunity to Type VII Collagen: Epidermolysis Bullosa Acquisita

Abstract

Epidermolysis bullosa acquisita (EBA) is an acquired, autoimmune, mechanobullous disease with clinical features reminiscent of genetic dystrophic epidermolysis bullosa (DEB). EBA patients have skin fragility, blisters, scars, and milia formation. DEB is due to a genetic defect in the gene-encoding type VII collagen, which makes anchoring fibrils, structures that attach the epidermis and its underlying basement membrane zone onto the papillary dermis. DEB patients have a decrease in normally functioning anchoring fibrils. EBA patients have the same problem, but their decrease in normally functioning anchoring fibrils is because of an abnormality in their immune system in which they produce anti-type VII collagen antibodies that attack their anchoring fibrils. These IgG anti-type VII collagen antibodies are "pathogenic" because when injected into a mouse, the mouse develops an EBA-like blistering disease. EBA has several distinct clinical presentations. It can present with features similar to DEB. It can also present with features reminiscent of bullous pemphigoid, cicatricial pemphigoid, Brunsting-Perry pemphigoid, or IgA bullous dermatosis. Treatment for EBA is unsatisfactory. Some therapeutic success has been reported with colchichine, dapsone, photopheresis, infliximab, and IVIG.

Clinical features and diagnosis of epidermolysis bullosa acquisita

“…This finding is similar to that of epidermolysis bullosa hereditaria and could explain skin fragility [111,112]. When performed from lesional skin, the cleavage plane can be demonstrated.…”

Epidermolysis bullosa acquisita: What’s new?

“…EBA patients have a decrease in normally functioning anchoring fibrils secondary to an abnormality in their immune system in which they produce ''pathogenic'' autoantibodies against type VII collagen. 13 …”

“…[8][9][10] Epidermolysis bullosa acquisita is a chronic blistering disease of skin and mucous membranes characterized by subepidermal blisters and tissue-bound as well as circulating autoantibodies to the dermalepidermal junction. [11][12][13] The circulating immunoglobulin (Ig)G antibodies in EBA react with a 290-kDa dermal protein, type VII collagen, which is the main constituent of anchoring fibrils located at the dermalepidermal junction, an adhesion molecule of the extracellular matrix in epithelial basement membranes. EBA is a rare disease with a prevalence of approximately 0.2 ⁄ million people.…”

Immune reactivity to type VII collagen: implications for gene therapy of recessive dystrophic epidermolysis bullosa

“…Despite the fact that the major type VII collagen auto-antigenic determinants are located in the NC1 domain, western blot studies have shown that other epitopes are positioned in the NC2 or in the triple-helical central domain, especially in childhood EBA. 24 Furthermore, our in silico prediction of type VII collagen peptide binding on different Human Leukocyte Antigen (HLA) molecules showed that antigenic epitopes were located on the entire type VII collagen molecule although consistently at a much higher density in the NC1 domain (data not shown). Owing to potential antibodies to epitopes outside of the NC1 domain, the earlier reported NC1-based ELISA, 25 which showed great sensitivity in EBA and Crohn's disease patients, is not suitable in the context of gene therapy for RDEB.…”