Fas-mediated cell death in toxic epidermal necrolysis and graft-versus-host disease: potential for therapeutic inhibition

Death receptors are a growing family of transmembrane proteins which can de tect the presence of specific extracellular death signals and rapidly trigg er cellular destruction by apoptosis. The best studied to date is Fas (CD95 ). Expression and signalling by Fas and its ligand (FasL, CD95L) is a tight ly regulated process essential for key physiological functions in a variety of organs, including the maintenance of immune homoeostasis. Recently, str ong evidence has shown that dysregulation of Fas expression and/or signalli ng contributes to the pathogenesis of toxic epidermal necrolysis and acute graft-versus-host disease. With these new developments, strategies for modu lating the function of Fas signalling have emerged and opened up novel ther apeutic possibilities. Specific blockade of Fas, for example with intraveno us immunoglobulin preparations containing specific anti-Fas antibodies, has shown great promise in the treatment of toxic epidermal necrolysis and may also be useful in the treatment of acute graft-versus-host disease. Furthe r developments in this field may have important clinical implications for t he treatment of such diseases.