cells in the periphery, in vitro assays of T cell functions show severely 
defective responses. The patient's cells may proliferate to a limited extent 
In response to strong mitogens (such as PHA). but show no response to soluble 
antigens such as tetanus toxoid or to allogeneic cells in in vitro assays. 
Immune responses in patients as well as peripheral T cell numbers may vary In 
patients over time. 
B lymphocyte numbers vary considerably more than do T cells In these 
patients. Although all patients have hypogammaglobulinemia. B cell counts can 
range from very low to elevated. Nonetheless, patients cannot mount an Immune 
response to immunizations. In in vitro studies, these B cells can sometimes be 
induced to secrete immunoglobulins If T cells from normal donors are added to 
the cultures. This observation suggests that the dysfunction of B cells is not 
due to any intrinsic defect, but rather to a lack of normal T cell help. 
Several objective measures of disease activity are available to permit 
monitoring the effects of gene therapy. The simplest is the level of dAdo In 
the urine and in packed red blood cells of the patient. More sophisticated assays 
are the measurement of peripheral blood lymphocyte populations, in vitro T and 
B cell immune functions, antibody responses and delayed hypersensitivity skin 
reactions, and cellular ADA levels. The disease is sufficiently predictable 
that successful gene therapy would be apparent. However, the development of 
fully normal immune functions, even in a totally successful treatment, may take more 
than a year. 
3. Is the protocol designed to prevent all manifestations of the 
disease, to halt the progression of the disease after symptoms have 
begun to appear, or to reverse manifestations of the disease In 
seriously ill victims? 
Gene therapy for ADA deficiency, if successful, should correct all aspects 
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Recombinant DNA Research, Volume 12 
