The role of Fas and related death receptors in autoimmune and other disease states☆,☆☆,★
Section snippets
Fas/CD95: A death receptor in the TNF-receptor superfamily
The Fas receptor was first identified by antibodies that induced rapid cell death. Treatment of susceptible cells with these antibodies induced all the hallmarks of apoptosis (ie, programmed cell death), a process originally defined in cells dying during normal development or after induction with chemotherapeutic agents, glucocorticoids, or γ-irradiation.1 Unlike cells dying by necrosis, in which the intracellular contents of the cell are released into the environment after membrane rupture,
THE ROLE OF FAS/FAS LIGAND INTERACTIONS IN AUTOIMMUNE AND OTHER DISEASE STATES
The role of the Fas receptor in regulating the human immune response and in the evolution of clinical disease is being actively investigated. The recent identification of the autoimmune lymphoproliferative syndrome (ALPS) as a disorder of defective lymphocyte apoptosis provides definitive evidence that directly links Fas receptor dysfunction with specific clinical and laboratory findings. Altered Fas or Fas ligand function may contribute to other human autoimmune, infectious, and malignant
THE FAS/FAS LIGAND SYSTEM IN DIAGNOSIS AND THERAPY
The interest in the Fas pathway, together with the availability of tests for soluble Fas and soluble Fas ligand, have stimulated investigation into the potential utility of these assays in a large array of human disorders. Overall, it appears that soluble Fas and Fas ligand are increased in clinical states of immune activation. As such, these tests do not appear to provide significant advantage over a variety of other nonspecific markers of immune activation. However, in certain circumstances,
Acknowledgements
We thank Dr Michael Lenardo for discussion and critique of the manuscript and Drs Stephen Straus and Elaine Jaffe for the CT scan and pathology source material.
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Drs Siegel and Fleisher prepared this manuscript in their private capacity, and no official endorsement or support by the National Institutes of Health should be inferred.
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Reprint requests: Thomas A. Fleisher, MD, Bldg 10, Rm 2C306, 10 Center Dr, MSC 1508, Bethesda, MD 20892-1508.
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