Junctional epidermolysis bullosa (JEB) is a heterogeneous group of rare inherited skin disorders in which defects in cell adhesion components cause incomplete formation of hemidesmosomes. We have immunohistochemically examined the skin from ten JEB patients (JEB gravis, n = 4; JEB mitis, n = 3; JEB plus pyloric atresia [JEB/PA], n = 3) using monoclonal antibodies specific for the integrin adhesion receptors α3β1 and α6β4, and for the α3, β3, and γ2 subunits of the basement membrane ligand, laminin 5. Consistent with our previous reports, only the JEB gravis patients without associated pyloric atresia expressed reduced or absent epitopes for laminin-5 subunits in their epidermal basement membrane. In contrast, all three JEB/PA cases showed abnormalities in integrin α6β4, but not in laminin 5, expression in their basal epidermal cells. Integrin β4 subunit was undetectable in the biopsied epidermis of these JEB/PA individuals using five different monoclonal antibodies that recognize both intra- and extracellular epitopes. The absence of the β4 subunit in the epidermis of JEB/PA specimens was confirmed by Western blot analysis of tissue extracts. Epidermal expression of the integrin α6 subunit was variable in the JEB/PA patients. Abnormal integrin α6β4 expression may define the subset of JEB cases with pyloric atresia. These results strongly implicate a functional role for α6β4 in the formation of complete hemidesmosomes and in stable adhesion of basal keratinocytes to the basement membrane in vivo.
|Number of pages||8|
|Journal||Journal of Investigative Dermatology|
|Publication status||Published - Sep 1996|
- Cell adhesion
- Vesiculobullous skin diseases
ASJC Scopus subject areas