Abstract |
Two children with adenosine deaminase ( ADA) deficiency and combined immunodeficiency disease were given parenteral deoxycytidine in order to reverse the severe T-cell immunodeficiency associated with this disease. One patient received a total of three courses of parenteral deoxycytidine. On two occasions deoxycytidine (50 mg/kg/day) was infused intravenously continuously for 2 weeks. During one of the infusions she received the deoxycytidine deaminase inhibitor tetrahydrouridine (THU). Steady-state levels of plasma deoxycytidine increased 4-fold with THU. RBC dCTP/dATP increased more than 10-fold after 48 hr of deoxycytidine infusion. Immunologic studies following the intravenous infusion of deoxycytidine showed transient improvement in T-cell immunity. The third course of deoxycytidine (50 mg/kg/day) was administered subcutaneously during a 10-hr night-time infusion. After 6 and 12 weeks of nightly subcutaneous infusions, there was minimal improvement in the in vitro immunologic studies and no clinical improvement. The second patient received a single 2-week course of continuous intravenous deoxycytidine (50 mg/kg/day) following which there was no significant change in T-cell immunity. This study defines some of the pharmacologic parameters of human deoxycytidine metabolism and suggests that some patients with ADA deficiency may respond to deoxycytidine therapy with improvement in T-cell-mediated immunity, although the changes are small and the effect on clinical status appears to be limited.
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Authors | M J Cowan, D W Wara, A J Ammann |
Journal | Clinical immunology and immunopathology
(Clin Immunol Immunopathol)
Vol. 37
Issue 1
Pg. 30-6
(Oct 1985)
ISSN: 0090-1229 [Print] United States |
PMID | 3161676
(Publication Type: Case Reports, Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Deoxycytosine Nucleotides
- Deoxycytidine
- 2'-deoxycytidine 5'-triphosphate
- Nucleoside Deaminases
- Adenosine Deaminase
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Topics |
- Adenosine Deaminase
(deficiency, metabolism)
- Child, Preschool
- Deoxycytidine
(blood, therapeutic use)
- Deoxycytosine Nucleotides
(blood)
- Erythrocytes
(analysis, enzymology)
- Female
- Humans
- Immunologic Deficiency Syndromes
(drug therapy)
- Infant
- Leukocyte Count
- Lymphocyte Culture Test, Mixed
- Male
- Nucleoside Deaminases
(deficiency)
- T-Lymphocytes
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