This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lainka, E.
Right arrow Articles by Niehues, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lainka, E.
Right arrow Articles by Niehues, T.

 Previous Article  |  Next Article 

Clinical and Diagnostic Laboratory Immunology, July 2005, p. 861-866, Vol. 12, No. 7
1071-412X/05/$08.00+0     doi:10.1128/CDLI.12.7.861-866.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Polyethylene Glycol-Conjugated Adenosine Deaminase (ADA) Therapy Provides Temporary Immune Reconstitution to a Child with Delayed-Onset ADA Deficiency

Elke Lainka,1* Michael S. Hershfield,2 Ines Santisteban,2 Pawan Bali,2 Annette Seibt,1 Jennifer Neubert,1 Wilhelm Friedrich,3 and Tim Niehues1

Department of Paediatric Oncology, Haematology and Immunology, Children's Hospital of the Heinrich Heine University, Düsseldorf, Germany,1 Department of Medicine, Box 3049, Duke University Medical Center, Durham, North Carolina,2 Paediatric Immunology Unit, Children's Hospital of the University of Ulm, Ulm, Germany3

Received 20 February 2005/ Returned for modification 17 March 2005/ Accepted 11 April 2005

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/µl; CD8, 459/µl), B cells (16/µl), and NK cells (55/µl). 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.

* Corresponding author. Mailing address: Uniklinikum Essen, Kinderheilkunde, Hufelandstr. 55, 45122 Essen, Germany. Phone: 49 201 723 3350. Fax: 49 201 723 2372. E-mail: elke.lainka{at}uni-essen.de.

Clinical and Diagnostic Laboratory Immunology, July 2005, p. 861-866, Vol. 12, No. 7
1071-412X/05/$08.00+0     doi:10.1128/CDLI.12.7.861-866.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»