Epidermolysis bullosa acquisita (EBA) is a chronic autoimmune subepidermal blistering disease of the skin and mucus membranes. Epidermolysis bullosa acquisita is caused by antibodies targeting type VII collagen, the major component of anchoring fibrils that connect the basement membrane to dermal structures. Epidermolysis bullosa acquisita (EBA) is a subepidermal bullous dermatosis of a result of its resemblance to hereditary forms of epidermolysis bullosa (HEB). Epidermolysis bullosa acquisita is a chronic subepidermal blistering disease associated with autoimmunity to type VII collagen within anchoring fibril structures.


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Clinical Presentation, Pathogenesis, Diagnosis, and Treatment of Epidermolysis Bullosa Acquisita

In animal models of AIBD, including pemphigus, bullous pemphigoid, and EBA, mice are completely blocked from disease induction [ 9394 ]. This protection can however be overridden by the transfer of excess amounts of antibodies [ 94 ].

Mechanisms of Autoantibody-Induced Tissue Injury Experiments employing several model systems have identified several cellular and molecular requirements for autoantibody-induced tissue injury in EBA.

This, for example, includes neutrophils, Fc receptors, complement activation, epidermolysis bullosa acquisita cytokines. While the contribution of each of these cells and molecules has been well documented, the exact timely and spatial sequence of events leading to blister formation has not been determined in detail.

Based on the current understanding of EBA pathogenesis, autoantibody-induced tissue injury in EBA can be divided into the following events: In line, large differences in clinical disease severity were observed after the transfer of anti-COL7 IgG into different mouse strains.

Overall, this points towards a yet to be determined genetic control of autoantibody-induced tissue injury in experimental EBA. This assumption is further supported by the observation of a high variation of skin blistering in outbred AIL mice after the epidermolysis bullosa acquisita of anti-COL7 IgG [ 66 ].

To further define the kinetics of anti-COL7 IgG deposition to the skin, autoantibodies were fluorescently labeled. These labeled anti-COL7 autoantibodies fully retained their ability to induce blistering in mice. These fluorescently labeled anti-COL7 autoantibodies epidermolysis bullosa acquisita i.

Within minutes after i. To study clearance rates of circulating and tissue-bound autoantibodies to COL7 in experimental EBA, retention times of diaplacentally transmitted anti-COL7 autoantibodies in serum and in skin were investigated.

Immediately after birth, comparable levels of pathogenic antibody concentrations were observed in maternal and neonatal mice. The clearance time of skin-bound autoantibodies was twice as long 8 weeks as that of circulating autoantibodies weeks.

Epidermolysis bullosa acquisita - Wikipedia

Interestingly, despite IgG and complement C3 deposition along the dermal-epidermal junction in the neonatic mice, epidermolysis bullosa acquisita histological, or clinical alterations were observed [ 46 ]. In addition to the skin, immunoperoxidase and immunofluorescence staining analyses found COL7 expression to be confined to the basement membranes beneath other stratified squamous epithelia; for example, oesophagus, buccal, anal, and vaginal mucosae, but not in colonic mucosa [ 2627 ].

On the contrary, others noted scattered COL7 staining in colonic epithelium and in epidermolysis bullosa acquisita small intestinal epithelial basement membrane [ 9798 ]. Furthermore, anchoring fibrils were detected by electron microscopy in the intestine [ 97 ], and COL7 expression was detected in oesophagus and colon [ 4199 ].

Of note, COL7 expression decreases from proximal to distal parts of the gastrointestinal tract [ 3 ].

F ab epidermolysis bullosa acquisita effects on blister formation have been described in bullous pemphigoid, for example, a weakening of cell attachment after the binding of anti-BP antibodies to keratinocytes [ — ]. In contrast, no data on F ab -mediated effects of anti-COL7 antibodies on keratinocyte adhesiveness has been reported.

Epidermolysis bullosa acquisita

As the NC1 domains multiple binding sites to epidermolysis bullosa acquisita proteins located within the dermal-epidermal junction, it seems plausible that autoantibody binding interferes with these interactions [ 70].

This may explain the pathogenesis of noninflammatory, mechanobullous EBA; however, this assumption needs to be epidermolysis bullosa acquisita confirmed. Several lines of evidence suggest that the Fc portion of anti-COL7 antibodies is a key molecular prerequisite to initiate blister formation.


In vitro, only IgG, but not F ab 2 fragments, directed to COL7 induced dermal-epidermal separation when incubated on cryosections of human skin, followed by the addition of neutrophils from healthy donors [ 60 ]. Furthermore, not all isoclasses of anti-COL7 have the potential to induce dermal-epidermal separation.

Similar observations are made in mice. While injection of rabbit anti-COL7 IgG induces skin blistering, the administration of corresponding F ab 2 fragments causes no pathology, despite binding to the dermal-epidermal junction [ 44 ]. epidermolysis bullosa acquisita


The absence of skin lesions in mice injected with chicken anti-mouse COL7 IgY, which does not bind murine complement and Fc receptors, further underlines the importance of Fc-Fc receptor interactions for blister formation in experimental EBA [ ]. Recent attention has also been attributed to the epidermolysis bullosa acquisita status epidermolysis bullosa acquisita IgG, as this has been demonstrated to have a great impact on IgG function [ ].

Epidermolysis bullosa acquisita | DermNet New Zealand

Epidermolysis bullosa acquisita exact timely and special resolution of events occurring after autoantibody binding in EBA has yet to be defined. The current concept of antibody-induced tissue injury is that epidermolysis bullosa acquisita a multistep, directed, but not linear, process leading from antibody binding to blister formation.

So far, the following cells and molecules have been identified to contribute to blister formation in experimental EBA: