{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T09:17:40Z","timestamp":1782811060355,"version":"3.54.5"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2005,7,1]],"date-time":"2005-07-01T00:00:00Z","timestamp":1120176000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Clin Vaccine Immunol"],"published-print":{"date-parts":[[2005,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>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 \u201cdelayed-onset\u201d ADA deficiency and marked immunodysregulation. Pretreatment lymphopenia affected T cells (CD4, 150\/\u03bcl; CD8, 459\/\u03bcl), B cells (16\/\u03bcl), and NK cells (55\/\u03bcl). 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.<\/jats:p>","DOI":"10.1128\/cdli.12.7.861-866.2005","type":"journal-article","created":{"date-parts":[[2005,7,7]],"date-time":"2005-07-07T19:08:21Z","timestamp":1120763301000},"page":"861-866","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["Polyethylene Glycol-Conjugated Adenosine Deaminase (ADA) Therapy Provides Temporary Immune Reconstitution to a Child with Delayed-Onset ADA Deficiency"],"prefix":"10.1128","volume":"12","author":[{"given":"Elke","family":"Lainka","sequence":"first","affiliation":[{"name":"Department of Paediatric Oncology, Haematology and Immunology, Children's Hospital of the Heinrich Heine University, Du\u0308sseldorf, Germany"},{"name":"Department of Medicine, Box 3049, Duke University Medical Center, Durham, North Carolina"},{"name":"Paediatric Immunology Unit, Children's Hospital of the University of Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Hershfield","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology, Haematology and Immunology, Children's Hospital of the Heinrich Heine University, Du\u0308sseldorf, Germany"},{"name":"Department of Medicine, Box 3049, Duke University Medical Center, Durham, North Carolina"},{"name":"Paediatric Immunology Unit, Children's Hospital of the University of Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Santisteban","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology, Haematology and Immunology, Children's Hospital of the Heinrich Heine University, Du\u0308sseldorf, Germany"},{"name":"Department of Medicine, Box 3049, Duke University Medical Center, Durham, North Carolina"},{"name":"Paediatric Immunology Unit, Children's Hospital of the University of Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawan","family":"Bali","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology, Haematology and Immunology, Children's Hospital of the Heinrich Heine University, Du\u0308sseldorf, Germany"},{"name":"Department of Medicine, Box 3049, Duke University Medical Center, Durham, North Carolina"},{"name":"Paediatric Immunology Unit, Children's Hospital of the University of Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Seibt","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology, Haematology and Immunology, Children's Hospital of the Heinrich Heine University, Du\u0308sseldorf, Germany"},{"name":"Department of Medicine, Box 3049, Duke University Medical Center, Durham, North Carolina"},{"name":"Paediatric Immunology Unit, Children's Hospital of the University of Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Neubert","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology, Haematology and Immunology, Children's Hospital of the Heinrich Heine University, Du\u0308sseldorf, Germany"},{"name":"Department of Medicine, Box 3049, Duke University Medical Center, Durham, North Carolina"},{"name":"Paediatric Immunology Unit, Children's Hospital of the University of Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelm","family":"Friedrich","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology, Haematology and Immunology, Children's Hospital of the Heinrich Heine University, Du\u0308sseldorf, Germany"},{"name":"Department of Medicine, Box 3049, Duke University Medical Center, Durham, North Carolina"},{"name":"Paediatric Immunology Unit, Children's Hospital of the University of Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Niehues","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology, Haematology and Immunology, Children's Hospital of the Heinrich Heine University, Du\u0308sseldorf, Germany"},{"name":"Department of Medicine, Box 3049, Duke University Medical Center, Durham, North Carolina"},{"name":"Paediatric Immunology Unit, Children's Hospital of the University of Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"5562","DOI":"10.4049\/jimmunol.171.10.5562","volume":"171","year":"2003","unstructured":"Aldrich, M. 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