Underexpression and overexpression of Fas and Fas ligand: a double-edged sword.
OBJECTIVE
To compare autoimmune lymphoproliferative syndrome (ALPS) and Stevens-Johnson syndrome (SJS) with respect to the defects in Fas- and Fas ligand (FasL)-mediated apoptosis.


METHODS
Selected reviews, case reports, and original studies were searched in PubMed and MEDLINE for the keywords ALPS, SJS, Fas, FasL, and apoptosis.


METHODS
Case reports of ALPS and SJS were selected as examples of Fas- and FasL-mediated diseases. In addition, we selected articles that examined the pathophysiology of apoptosis in the context of Fas-FasL interaction.


RESULTS
Failure to initiate apoptosis of abnormal T lymphocytes occurs in such diseases as ALPS, leading to the accumulation of double negative T cells with an increase in autoimmunity. In contrast to apoptotic failure, SJS is associated with a pathological increase in programmed keratinocyte cell death.


CONCLUSIONS
The consequences of dysregulated Fas- and FasL-mediated apoptosis leads to self-reactivity, malignant transformation, and immune dysfunction. An understanding of underlying mechanisms and qualitative assessment of Fas and FasL may have clinical benefits when control of these homeostatic mechanisms is in question.
Randhawa
Shahid R
SR
Department of Pediatrics, Section of Allergy and Immunology, LSU Health Sciences Center, Shreveport, Louisiana 71130, USA.
Chahine
Bassem G
BG
Lowery-Nordberg
Mary
M
Cotelingam
James D
JD
Casillas
Adrian M
AM
D000328:Adult; D017209:Apoptosis / Q000502:physiology; D056735:Autoimmune Lymphoproliferative Syndrome / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D013262:Stevens-Johnson Syndrome / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D053222:Fas Ligand Protein; D019014:fas Receptor