Keratinocyte apoptosis and p53 expression in cutaneous lupus and dermatomyositis

Keratinocyte apoptosis mag be induced by ultraviolet-B radiation and repres ents a potential source of fragmented autoantigens in autoimmune diseases, This study investigates whether excessive keratinocyte apoptosis occurs in the skin lesions of cutaneous lupus (CLE) and dermatomyositis (DM) and the potential mechanisms responsible for this phenomenon. Skin biopsies hare be en studied from 19 patients with CLE and DM, eight with scleroderma, and fi ve healthy controls, Apoptosis was detected by in situ end-labelling of fra gmented DNA. The expression of Bcl-2, PCNA, p53, and Ki-67 proteins was stu died by immunohistochemistry. In DM and CLE skin, the number of apoptotic k eratinocytes was significantly increased (p=0.008) compared with normal ski n. In both diseases, a large accumulation of apoptotic keratinocytes and ap optotic bodies was present in the disrupted basal zone. Unlike normal skin, a large number of keratinocytes, particularly those morphologically apopto tic, expressed p53 protein. A significant increase in the number of prolife rating Ki-67 positive (p=0.0007) and PCNA-positive (p=0.0008) nuclei was al so observed. In both CLE and DM, exaggerated and inappropriate keratinocyte apoptosis occurs. It is associated with increased expression of p53 and PC NA. This suggests that normal solar radiation alone or in combination with additional local factors induces DNA damage and excessive keratinocyte apop tosis in these autoimmune diseases of the skin, Apoptosis can mediate the s evere epidermal lesions observed in both diseases and the release of fragme nted autoantigens into the dermis, Copyright (C) 1999 John Wiley & Sons, Lt d.