Epidermolysis Bullosa Acquisita

Abstract

In mouse models, loss of integrin I±[alpha]3 caused abnormal kidney and lung organogenesis and skin fragility, but no corresponding human disease has been known. We identified three patients with homozygous mutations in the integrin I±[alpha]3 gene, who had a multiorgan disorder including congenital nephrotic syndrome, interstitial lung disease and epidermolysis bullosa. The renal and respiratory features predominated and determined the lethal course of the disease. Although skin fragility was mild, it provided clues to the diagnosis. Immunofluorescence staining of the patient's skin demonstrated junctional cleavage with laminin-332 located both at the roof and the base of the blister. Transmission electron microscopy revealed abnormalities of the dermo-epidermal junction, with a thin and discontinuous lamina densa between the hemidesmosomes. In all affected organs, disrupted basement membrane structures led to compromised barrier functions. These explained the pathogenesis of the disorder in part, but further patients must be investigated for full understanding of the disease mechanisms.