Apoptosis in the Pathogenesis of Cutaneous Lupus Erythematosus

Abstract

Defective regulation of apoptosis may play a role in the development of autoimmune diseases such as systemic lupus erythematosus, in which the skin is a prominent target. To our knowledge, however, the nature of epidermal changes in cutaneous lupus erythematosus (LE) has not previously been investigated. We investigated the involvement of apoptosis in cutaneous LE. A total of 44 lesional skin samples from patients with cutaneous LE, 44 skin samples from patients with scleroderma, five skin specimens from patients suffering from dermatomyositis, and 13 normal skin samples were stained immunohistochemically with monoclonal antibodies to Ki-67, p53 (DO-7), and bcl-2. The lesional skin from cutaneous LE, except LE profundus, showed a marked increase in Ki-67- and p53-positive keratinocytes, which were predominantly located in the basal layer of the epidermis and follicle, and a drastic reduction in the number of bcl-2-positive cells localized in the basal cell compartment. With TdT-mediated dUTP-biotin nick end-labeling staining, we demonstrated that extensive apoptosis occurred in almost the whole epidermis of cutaneous LE, except in cases of LE profundus. This abnormal expression of Ki-67, p53, and bcl-2 and the occurrence of apoptosis in the epidermis was also observed in epidermis from patients with dermatomyositis, but not in that from patients with scleroderma.

Accumulation of apoptotic cells in the epidermis of patients with cutaneous lupus erythematosus after ultraviolet irradiation

“…Interestingly, nonlesional skin from patients with CLE also revealed a significantly higher count of epidermal apoptotic nuclei compared with normal skin. This finding of increased apoptosis in skin biopsy specimens from primary lesions of patients with CLE is in accordance with the findings in several published reports (45)(46)(47). In contrast to our study, in some of these studies apoptotic keratinocytes were observed in the entire epidermis, which might be explained by background labeling when performing the TUNEL technique under more relaxed conditions (48,49).…”

Cell Death in Human Lung Transplantation: Apoptosis Induction in Human Lungs During Ischemia and After Transplantation

“…9 An important morphologic distinction from necrosis lies in the fact that apoptotic cell death lacks inflammation. 12 There are strong indications that apoptosis plays an important regulatory role in various disease processes such as cancer, 13,14 autoimmune diseases, 15,16 and others. [17][18][19][20][21] Increasing evidence suggests that alterations in the genetic control of cell survival and elimination seem to be important regulators in these disease states.…”

Cutaneous distribution of plasmacytoid dendritic cells in lupus erythematosus. Selective tropism at the site of epithelial apoptotic damage

“…3B). CD8 cytotoxic T cells recruited to lesional skin by IFN-inducible chemokines (Blomberg et al 2001;Farkas et al 2001;Wenzel et al 2005), are retained the major responsible for this damage via the perforin and granzyme pathway (Blanco et al 2005), resulting in necrosis in basal and spinous epidermal layers (Chung et al 1998). It has been found that PDC strongly express granzyme B (GrB) either in lymphoid organs and inflamed skin (Rissoan et al 2002;Santoro et al 2005).…”