polyethylene glycol-conjugated adenosine deaminase (ADA) therapy provides temporary immune reconstitution to a child with delayed-onset ADA deficiency.
We describe the effects of polyethylene glycol-conjugated adenosine deaminase (ADA) replacement therapy on lymphocyte counts, activation, apoptosis, proliferation, and cytokine secretion in a 14-month-old girl with "delayed-onset" ADA deficiency and marked immunodysregulation. Pretreatment lymphopenia affected T cells (CD4, 150/microl; CD8, 459/microl), B cells (16/microl), and NK cells (55/microl). T cells were uniformly activated and largely apoptotic (CD4, 59%; CD8, 82%); and T-cell-dependent cytokine levels in plasma were elevated, including the levels of interleukin 2 (IL-2; 26 pg/ml), IL-4 (81 pg/ml), IL-5 (46 pg/ml), gamma interferon (1,430 pg/ml), tumor necrosis factor alpha (210 pg/ml), and IL-10 (168 pg/ml). Mitogen-stimulated peripheral blood mononuclear cells show reduced IL-2 secretion and proliferation. During the first 5 months of therapy there was clinical improvement and partial immune reconstitution, with nearly normal lymphocyte subset numbers, reduced T-cell activation and CD4-cell apoptosis, and decreased plasma cytokine levels. In parallel, IL-2 secretion and the lymphocyte mitogenic response improved. Between 4 and 7 months, immunoglobulin G antibodies to bovine ADA developed and resulted in the complete reversal of immune recovery.
Uniklinikum Essen, Kinderheilkunde, Hufelandstr. 55, 45122 Essen, Germany. elke.lainka@uni-essen.de
Elke
E
Lainka
Michael S
MS
Hershfield
Ines
I
Santisteban
Pawan
P
Bali
Annette
A
Seibt
Jennifer
J
Neubert
Wilhelm
W
Friedrich
Tim
T
Niehues
D000243:Adenosine Deaminase / Q000008:administration & dosage* / Q000172:deficiency; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D004800:Enzymes, Immobilized / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007223:Infant; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000097:blood / Q000188:drug therapy*; D016176:T-Lymphocyte Subsets / Q000378:metabolism
D016207:Cytokines; D004800:Enzymes, Immobilized; D011092:Polyethylene Glycols; D000243:Adenosine Deaminase