APOPTOSIS IN THE PATHOGENESIS OF CUTANEOUS LUPUS-ERYTHEMATOSUS

Defective regulation of apoptosis may play a role in the development o f autoimmune diseases such as systemic lupus erythematosus, in which t he skin is a prominent target. To our knowledge, however, the nature o f epidermal changes in cutaneous lupus erythematosus (LE) has not prev iously been investigated. We investigated the involvement of apoptosis in cutaneous LE, A total of 44 lesional skin samples from patients wi th cutaneous LE, 44 skin samples from patients with scleroderma, five skin specimens from patients suffering from dermatomyositis, and 13 no rmal skin samples were stained immunohistochemically with monoclonal a ntibodies to Ki-67, p53 (DO-7), and bcl-2. The lesional skin from cuta neous LE, except LE profundus, showed a marked increase in Ki-67- and p53-positive keratinocytes, which were predominantly located in the ba sal layer of the epidermis and follicle, and a drastic reduction in th e number of bcl-2-positive cells localized in the basal cell compartme nt. With TdT-mediated dUTP-biotin nick end-labeling staining, we demon strated that extensive apoptosis occurred in almost the whole epidermi s of cutaneous LE, except in cases of LE profundus. This abnormal expr ession of Ki-67, p53, and bcl-2 and the occurrence of apoptosis in the epidermis was also observed in epidermis from patients with dermatomy ositis, but not in that from patients with scleroderma.