Abstract
Deficiency of adenosine deaminase (ADA) is associated with a form of severe combined immunodeficiency disease (SCID). Enzyme replacement therapy using red blood cells as a source of ADA restores the ability of ADA deficient SCID lymphocytes to respond to mitogens in vitro but does not increase ADA activity within these cells. The availability of ADA deficient lymphocytes capable of responding to mitogens permitted us to study the effects of various pharmacological agents in order to gain a better understanding of the metabolic basis of this immunodeficiency disease.
Phytohemagglutinin (PHA)-induced proliferation of lymphocytes from an ADA deficient SCID patient were significantly more sensitive to inhibition by theophylline (p<.01), norepinephrine (p<.05) and prostaglandins E1 and E2 (p<.01 and < .0005, respectively) than lymphocytes from individuals with normal ADA activity. In contrast, there was no significant difference (p>.4) in sensitivity to inhibition by adenosine at concentrations less than 100 μ molar. Since theophylline, norepinephrine and prostaglandins E1 and E2 elevate intracellular cAMP concentrations, which inhibits many lymphocyte functions, these data suggest that defective lymphocyte proliferation in ADA deficiency may be due to an increased potential for excessive cAMP synthesis. Drugs capable of inhibiting cAMP synthesis or enhancing its catabolism may be useful in the therapy of this disorder. Extracellular adenosine probably plays a minor role, if any, in causing this immunodeficiency.
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Polmar, S., Wetzler, E. & Stern, R. IMMUNOPHARMACOLOGIC STUDIES OF ADENOSINE DEAMINASE DEFICIENT LYMPHOCYTES. Pediatr Res 11, 492 (1977). https://doi.org/10.1203/00006450-197704000-00733
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DOI: https://doi.org/10.1203/00006450-197704000-00733
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