Antigenic expression of integrin alpha 6 beta 4 in junctional epidermolysis bullosa

Integrin alpha 6 beta 4 is a major component of hemidesmosomes, considered to play a central role in the adhesion of basal epidermal cells to the underlying dermis. It is therefore of considerable interest in the study of the aetiology of inherited blistering disorders. We have examined the immunohistochemical characteristics of skin from 16 patients with epidermolysis bullosa using two antibodies directed against epitopes on the beta 4 subunit of alpha beta 4 integrin (G71, 3E1), one antibody directed against an epitope on the alpha 6 subunit (GoH3), GB3 an antibody for nicein, and LH7.2, an anticollagen type VII antibody. All 10 patients with junctional epidermolysis bullosa showed markedly reduced or no immunoreactivity with G71. These patients included two with GB3-positive junctional epidermolysis bullosa associated with pyloric atresia, and four with other subtypes. By contrast, five patients with dystrophic epidermolysis bullosa and one patient with epidermolysis bullosa simplex showed normal immunoreactivity with G71. In this study, G71 is shown to have a high specificity and sensitivity for the diagnosis of junctional epidermolysis bullosa. Immunoreactivity with 3E1 and GoH3 was normal in most patients, consistent with published reports showing normal immunoreactivity with other beta 4 and alpha 6 subunit antibodies. The data suggest a modification of the beta 4 subunit of integrin alpha 6 beta 4 at the dermo-epidermal junction in junctional epidermolysis bullosa.