Changes in the expression of integrins and basement membrane proteins in benign mucous membrane pemphigoid

OBJECTIVE: To determine the location of the subepi-thelial split in benign mucous membrane pemphigoid (BMMP) and its relationship to the anchoring filaments and their receptors. MATERIALS AND METHODS: Frozen sections of lesional and perilesional oral mucosa from 10 cases of BMMP were stained, using an immunofluorescence method, for the β₁, β₄, α₃ and α₆ integrin subunits and for their ligands, laminin I and laminin V (kalinin). In all cases the diagnosis was confirmed by the demonstration of linear staining for IgG at the basement membrane zone. Six specimens of normal mucosa were stained for comparison. RESULTS Staining for integrins, laminin and kalinin in perilesional mucosa was similar to normals, although one case showed loss of α₆ and β₄. In lesional mucosa, laminin and kalinin showed strong linear staining localised to the floor of the bullae. The α₆ and β₄ subunits were expressed only on the roof of the bullae but staining was weak and patchy with areas of loss. In some sections a₆ showed a punctate intracellular distribution similar to IgG. The distribution of α₃ and β₁ was similar to that seen in normals. CONCLUSIONS: In all cases kalinin was found on the connective tissue side of the lesions and α₆β₄ localised to the epithelial side. This shows that the split occurs at a location which separates anchoring filaments from the hemidesmosomes. Loss of the α₆β₄ integrin in the lesions and the similar intracellular staining of α₆ and IgG, suggest that disruption of hemidesmosomes may be a key event in the immunopathogenesis of the lesions and that the α₆ integrin subunit is a potential antigen in oral mucosal BMMP.