The Wiskott-Aldrich syndrome: Studies of lymphocytes, granulocytes, and platelets

Morphological, functional, and kinetic studies of lymphocytes, granulocytes, and platelets were carried out in three boys with classic and one with an 'attenuated form' of the Wiskott-Aldrich syndrome (WAS). Lymphocyte counts, adequate during infancy, declined and were below normal by age 6. In vitro lymphocyte responses to irradiated allogeneic cells were uniformly abnormal: titers were low, immunologic memory was depressed, and the switch from IgM to IgG was impaired. The three boys with classic WAS did not respond to polysaccharide antigens. Neutrophils responded poorly to chemoattractants and WAS sera generated less chemotactic activity than normal sera. A heat-stable inhibitor of chemotaxis was demonstrated in one patient's serum. Thrombocytopenia with platelets of half-normal size was found in all patients. Megakaryocyte cytoplasmic mass (a direct measure of marrow platelet production capacity) was normal, and the modest reductions in platelet survivals found (mean half-life, 5 days) were not sufficient to explain the degree of thrombocytopenia. Platelet turnover, which reflects the production of viable platelets, was 30% of expected, indicating that thrombocytopenia was due to ineffective thrombocytopoiesis. Similar measurements of platelets from mothers of our WAS patients were normal.