Spontaneous apoptosis in lymphocytes from patients with Wiskott-Aldrich syndrome: Correlation of accelerated cell death and attenuated Bcl-2 expression

Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characteri zed by thrombocytopenia, eczema, and a progressive deterioration of immune function. WAS is caused by mutations in an intracellular protein, WASP, tha t is involved in signal transduction and regulation of actin cytoskeleton r earrangement. Because immune dysfunction In WAS may be due to an accelerate d destruction of lymphocytes, we examined the susceptibility to apoptosis o f resting primary lymphocytes isolated from WAS patients in the absence of exogenous apoptogenic stimulation. We found that unstimulated WAS lymphocyt es underwent spontaneous apoptosis at a greater frequency than unstimulated normal lymphocytes. Coincident with increased apoptotic susceptibility, WA S lymphocytes had markedly attenuated Bcl-2 expression, whereas Bar express ion did not differ. A negative correlation between the frequency of spontan eous apoptosis and the level of Bcl-2 expression was demonstrated. These da ta indicate that accelerated lymphocyte destruction by spontaneous inductio n of apoptosis may be one pathogenic mechanism by which the progressive imm unodeficiency in WAS patients develops. (C) 1999 by The American Society of Hematology.