Comparison of red cell transfusion and polyethylene glycol-modified adenosine deaminase therapy in an adenosine deaminase-deficient child: measurement of erythrocyte deoxyadenosine triphosphate as a useful tool.
The effect of red cell transfusion and polyethylene glycol-modified adenosine deaminase therapy on biochemical abnormalities, clinical status, and immunologic function in an adenosine deaminase-deficient child was investigated. After red cell transfusions, erythrocyte deoxyadenosine triphosphate (dATP) concentrations decreased about 95% and were closely related to adenosine deaminase activities; deoxyadenosine diphosphate concentrations decreased only approximately 30%. The evolution of dATP levels was also closely related to the improvement in clinical status of the patient. However, immune function was not restored. After polyethylene glycol-modified adenosine deaminase therapy, the concentration of erythrocyte dATP decreased to undetectable levels correlated with an increase of T lymphocyte counts and an increase of lymphocyte responses to mitogens. Immune functions were restored only when dATP levels were below 15 mumols/L. It appears that red cell transfusion therapy is not sufficiently effective to reduce and maintain erythrocyte dATP levels at values compatible with normal immune function. On the contrary, polyethylene glycol-modified adenosine deaminase therapy is a suitable treatment to reduce dATP levels to near undetectable values, allowing the immune function to be restored, dATP measurement is a very useful tool for monitoring and evaluating the degree of efficiency of therapy in adenosine deaminase deficiency.
Laboratoire de Biochimie, Hôpital Debrousse, Lyon, France.
C
C
Bory
R
R
Boulieu
G
G
Souillet
C
C
Chantin
M O
MO
Rolland
M
M
Mathieu
M
M
Hershfield
D000243:Adenosine Deaminase / Q000008:administration & dosage / Q000172:deficiency* / Q000627:therapeutic use; D001803:Blood Transfusion; D002675:Child, Preschool; D003838:Deoxyadenine Nucleotides / Q000097:blood*; D004341:Drug Evaluation; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000276:immunology / Q000628:therapy; D008214:Lymphocytes / Q000276:immunology; D009700:Nucleoside Deaminases / Q000172:deficiency*; D011092:Polyethylene Glycols
D003838:Deoxyadenine Nucleotides; D011092:Polyethylene Glycols; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; C026600:2'-deoxyadenosine triphosphate