Abstract
Among patients with ADA deficiency, those with SCID have near complete absence of ADA, while some patients with severe T cell dysfunction but preservation of B cell function may have 1-3% of normal ADA activity in lymphoid cells. Patients with >5% of normal ADA activity in lymphoid cells have had no immune defect. We describe a patient with classical onset of SCID at 3 months, who was begun on red cell transfusions and immunoglobulin replacement therapy at 6 months of age. Despite long term survival, she remained severely lymphopenic and immune deficient. After starting PEG-ADA therapy at age 10 years her lymphocytes increased and became responsive to mitogens, and she developed in vivo B cell function. Just prior to starting PEG-ADA, unfractionated nucleated cells from her bone marrow were found to have 1000 nmol/h/mg protein). This observation was repeated with blood and marrow derived mononuclear cells and IL2-dependent T cells and T cell clones on 6 other occasions. HLA typing indicated the ADA+ T cells were the patient's own cells. T cell ADA had normal heat stability. Km, pl and was inhibited >99% by EHNA. In contrast to her T cells, 12 EBV transformed B cell clones from the patient had <0.3% of normal ADA activity. ADA+ T cells had normal T cell surface antigens and responsed in vitro to IL-2, mitogens, antigen and allogeneic cells. Important questions raised by these findings concern the molecular basis for the T cell ADA activity and the reason that these cells failed to proliferate and function more effectively in this patient in vivo. Acquisition of ADA activity by T lymphocyte precursor cells may not be sufficient to restore immune function in some ADA deficient patients. This possibility should be considered in view of proposals to treat ADA deficiency by somatic cell gene replacement.
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