The distribution and morphology of tonofilament (TF) clumps were examined by light and electron microscopy in skin samples from a total of 17 patients with the Dowling-Meara (DM) form of
epidermolysis bullosa simplex (EBS). TF clumps extending from the basal to the upper-spinous epidermal layer were seen in all lesional skin samples and in the majority of peri-lesional and non-lesional skin samples. TF clumps were also noted in adnexal epithelia, including outer hair root sheaths, sweat ducts, and sebaceous glands. Cultured keratinocytes from two patients also demonstrated characteristic TF clumps. All these epithelial cells have in common their expression of the
keratin pair K5 and K14. Post-embedding immunogold electron microscopy using
antibodies to K5, K14, and K10 showed similar expressed
keratins in DM-EBS skin from four patients compared with normal skin, with K5 and K14 predominantly in the basal cell layer and K10 in the suprabasal layers. The clumped TF in DM-EBS samples were labeled strongly with anti-K5 and K14
antibodies in the basal and suprabasal layers. In contrast, the suprabasal clumps were only slightly reactive with anti-K10
antibodies and labeling was usually restricted to the periphery of the clumps. We conclude that DM-EBS is associated with an intrinsic abnormality of the
keratin-filament network involving the K5 and K14 pair that is likely to result in impaired resistance of basal epidermal cells to external shearing forces, leading to the characteristic intraepidermal
blisters. DM-EBS may become the first
genetic skin disease to be recognized as having a specific
keratin abnormality.