Autoimmunity to Type VII Collagen: Epidermolysis Bullosa Acquisita

Abstract

Epidermolysis bullosa acquisita (EBA) is an acquired, mechanobullous disease characterized by autoimmunity to type VII collagen. Type VII collagen makes anchoring fibrils, structures that connect the epidermis and its underlying basement membrane zone to the papillary dermis. EBA patients exhibit skin fragility, blisters, scars and milia formation reminiscent of genetic dystrophic epidermolysis bullosa (DEB). DEB patients have diminutive or absent anchoring fibrils due to a genetic defect in the gene encoding type VII collagen. EBA patients have a decrease in normally functioning anchoring fibrils secondary to an abnormality in their immune system in which they produce 'pathogenic' IgG anti-type VII collagen antibodies. The pathogenicity of these autoantibodies has been demonstrated by passive transfer animal models, in which anti-type VII collagen antibodies injected into a mouse produced an EBA-like blistering disease in the animal. EBA has several distinct clinical presentations. It can present with features similar to DEB, bullous pemphigoid, cicatricial pemphigoid, Brunsting-Perry pemphigoid or IgA bullous dermatosis. Treatment for EBA is unsatisfactory, however, some therapeutic success has been reported with colchicine, dapsone, photophoresis, infliximab and intravenous immunoglobulin.

Amelioration of epidermolysis bullosa by transfer of wild-type bone marrow cells

“…In addition, the use of myeloablative therapy along with donor hematopoietic cell rescue would foster a state of immunologic tolerance to the wild-type protein rather than engender a foreign antigen immune response, analogous to the immune reactivity seen in the acquired autoimmune form of epidermolysis bullosa (epidermolysis bullosa acquisita). 40 The cause of death for untreated Col7a1 Ϫ/Ϫ mice is likely mucosal disruption with consequent weight loss and malnutrition. In support of this hypothesis, the clusters of donor GFP ϩ cells were seen in the submucosal layer of the tongue and the esophagus (Figure 3).…”

Pathogenicity of IgG subclass autoantibodies to type VII collagen: Induction of dermal–epidermal separation

“…EBA has several clinical presentations, mimicking other bullous skin diseases. The degree of skin inflammation differs between individual patients, with predominantly non-inflammatory mechanobullous forms or inflammatory variants resembling bullous pemphigoid [6]. Epitopes recognized by most EBA and BSLE patient autoantibodies were mapped to the aminoterminal non-collagenous domain 1 (NC1) of type VII collagen [3,7,8].…”

Development of NC1 and NC2 domains of Type VII collagen ELISA for the diagnosis and analysis of the time course of epidermolysis bullosa acquisita patients

“…Direct and indirect IF cannot differentiate EBA from bullous pemphigoid (BP) because IF shows linear deposits of IgG in the BMZ in both diseases. Salt-split skin IF is highly specific for the diagnosis of EBA [5,16], however it is not routinely performed in many centers. Immunoblot cannot detect autoantibodies against conformation-dependent epitopes because it uses denatured and reduced antigens as substrates.…”