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J Clin Invest. Aug 1981; 68(2): 413–421.
PMCID: PMC370813
Biochemical and Functional Abnormalities in Lymphocytes from an Adenosine Deaminase-deficient Patient during Enzyme Replacement Therapy
John J. Hutton and Dan A. Wiginton
Mary S. Coleman and Steven A. Fuller
Susan Limouze and Beatrice C. Lampkin
Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 78284
Audie L. Murphy Memorial Veterans Hospital, San Antonio, Texas 78284
Department of Biochemistry, University of Kentucky, Lexington, Kentucky 40536
Children's Hospital Medical Center, Cincinnati, Ohio 45229
Abstract
Biochemical and immunological properties of lymphocytes were measured repetitively over a period of 40 mo during enzyme replacement by transfusion in a child with adenosine deaminase (ADA) deficiency and severe combined immunodeficiency disease. Catalytically defective ADA protein is present in the child's cells. ADA activity in his lymphocytes is 7 nmol/min per 108 cells with 51 ng of ADA protein/108 cells by radioimmunoassay. ADA activities in normal cord and adult lymphocytes average 193 and 92 nmol/min per 108 cells, respectively, with 429 and 223 ng of ADA protein/108 cells. Deoxy(d)ATP accumulates in the patient's erythrocytes and lymphocytes. Transfusion of irradiated packed erythrocytes partially corrects the metabolic defects. Frank metabolic relapse occurs if transfusions are discontinued for several months. The amounts of dATP in erythrocytes and lymphocytes averaged 13 and 2 times normal, respectively, during periods when transfusions were administered every 2-4 wk. Deoxyguanosine triphosphate and deoxycytidine triphosphate in lymphocytes were normal on 11 occasions, but deoxyribosylthymine triphosphate was ninefold increased. On 11 occasions dATP was measured in lymphocytes and erythrocytes isolated simultaneously. There was a positive, but statistically insignificant, correlation between amounts of dATP in the two types of cells (r = 0.25,P > 0.1). The absolute peripheral lymphocyte count was correlated with the activity of ADA in circulating erythrocytes and with the response of lymphocytes to phytohemagglutinin (r = 0.64, P < 0.01; r = 0.49, P < 0.05). Response of lymphocytes to stimulation by phytohemagglutinin in vitro and absolute peripheral lymphocyte counts were not significantly correlated with levels of dATP in the erythrocyte or lymphocyte during periods of intensive therapy. Although there was objective improvement during enzyme replacement, the child remained immunodeficient and biochemically abnormal.
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