Open AccessPolyethylene Glycol-Conjugated Adenosine Deaminase (ADA) Therapy Provides Temporary Immune Reconstitution to a Child with Delayed-Onset ADA Deficiency
Author(s) -
Elke Lainka,
Michael S. Hershfield,
Inés Santisteban,
Pawan Bali,
Annette Seibt,
Jennifer Neubert,
Wilhelm Friedrich,
Tim Niehues
Publication year - 2005
Publication title -
clinical and vaccine immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.649
H-Index - 77
eISSN - 1556-6811
pISSN - 1556-679X
DOI - 10.1128/cdli.12.7.861-866.2005
Subject(s) - adenosine deaminase , cd8 , cytokine , immune system , adenosine deaminase deficiency , endocrinology , tumor necrosis factor alpha , medicine , lymphocyte , antibody , t cell , immunology , biology , microbiology and biotechnology , adenosine
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.