Keratinocyte injury in drug-induced toxic epidermal necrolysis: Simultaneous but distinct topographic expression of CD95R and calprotectin.
Keratinocyte injury in drug-induced toxic epidermal necrolysis (TEN) is attributed to a dysregulation in the complex apoptotic machinery. This study was performed to investigate some aspects of the apoptotic pathomechanism involving calprotectin and the CD95 receptor (CD95R, FasR) in TEN. The expression of these two molecules corresponds to calcium-dependent and calcium-independent processes, respectively. Biopsies were collected from blistering skin in 21 TEN patients and from clinically uninvolved skin in 16 of these patients. Immunohistochemistry was performed using specific antibodies directed to CD95R and calprotectin. Half (8/16) of the biopsy specimens taken from clinically uninvolved sites showed the expression of calprotectin throughout the epidermis or restricted to the suprabasal layers. In these samples, a strong CD95R immunoreactivity was often restricted to the basal layer (8/16). Calprotectin was present in all biopsies of bullous skin, especially in suprabasal layers (15/21) or throughout the epidermis (6/21). By contrast, the prominent expression of CD95R was confined almost exclusively to the basal layer (15/21), and more rarely throughout the epidermis (2/21), and it remained sometimes unexpressed (4/21). A clear-cut boundary was often present between the areas labeled by the two antibodies with exceptional overlap between them. The simultaneous expression of calprotectin and CD95R in TEN at distinct levels of the epidermis indicates that the pathomechanism leading to keratinocyte death does not belong to a single process in TEN. Their expression in clinically uninvolved skin suggests that these processes are early and widespread events in TEN.
Department of Dermatopathology, University Medical Center Sart Tilman, Liège, Belgium.
Philippe
P
Paquet
Gerald E
GE
Piérard
D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000235:genetics; D002118:Calcium / Q000502:physiology; D004817:Epidermis / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D039841:Leukocyte L1 Antigen Complex / Q000096:biosynthesis* / Q000235:genetics; D013262:Stevens-Johnson Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019014:fas Receptor / Q000096:biosynthesis* / Q000235:genetics
D000911:Antibodies, Monoclonal; D039841:Leukocyte L1 Antigen Complex; D019014:fas Receptor; D002118:Calcium