Molecular Mechanism(s) of Deoxyribonucleoside Toxicity in T-Lymphoblasts
The association of at least two inborn errors of purine metabolism with immunodeficiency diseases has made possible the investigation of these diseases at the molecular level. Adenosine deaminase (ADA) deficiency results in severe combined immunodeficiency disease with impairment of T- and B-lymphocyte function.1 Purine nucleoside Phosphorylase (PNP) deficiency has been associated with T-lymphocyte dysfunction in nine patients.2 The mechanism(s) whereby these enzyme deficiency states affect lymphocyte development and/or function has (have) not been fully elucidated. However, the recent findings of markedly elevated dATP levels in ADA-deficient erythrocytes3 and of dGTP levels in PNP-deficient erythrocytes4 provide support for the hypothesis that deoxyribonucleosides play an important role in the pathogenesis of the immune dysfunction in these two diseases and suggest that deoxyribonucleosides or their metabolites may be toxic to lymphoid cells.
KeywordsAdenosine Deaminase Ribonucleotide Reductase Severe Combine Immunodeficiency Purine Nucleoside Phosphorylase Severe Combine Immunodeficiency Disease
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- 3.M. S. Coleman, J. Donofrio, J. J. Hutton, L. Hahn, A. Daoud, B. Lampkin, and J. Dyminski, Identification and quantitation of adenine deoxynucleotides in erythrocytes of a patient with adenosine deaminase deficiency and severe combined immunodeficiency J. Biol. Chem. 253:1619–1626 (1978).PubMedGoogle Scholar
- 9.J. F. Henderson and A. R. P. Paterson, “Nucleotide Metabolism: An Introduction,” Academic Press, New York (1973).Google Scholar