Abstract
Wiskott-Aldrich syndrome (WAS) is an X-linked platelet/immunodeficiency disease. The affected gene encodes WASP, a multidomain protein that regulates cytoskeletal assembly in blood cells. Patients have recurring infections, and their lymphocytes exhibit deficient proliferative responses in vitro. We report an evaluation of peripheral blood lymphocytes of 27 WAS patients, aged one month to 55 years. Whereas NK cells were normal, a significant deficit of T and B lymphocytes was observed. The number of lymphocytes was already decreased in infant patients, suggesting deficient output. Both CD4 and CD8 T lymphocytes were affected; the decrease was most pronounced for naïve T cells. Naïve CD4 lymphocytes of patients showed normal expression of Bcl-2, and Ki-67, and normal survival in vitro, suggesting that their in vivo survival and proliferation are normal. The collective data suggest that the patients' lymphocyte deficit results from deficient output, likely due to abnormal lymphocyte maturation in the thymus and bone marrow. We propose that WASP plays an important role not only in the function of mature T lymphocytes, but also in the maturation of human T and B lymphocytes and that impaired lymphocyte maturation is central to the aetiology of WAS immunodeficiency.