| | |  | | | | Record from Web of Science® | | | | | | |
| T-LYMPHOCYTE ONTOGENY IN ADENOSINE-DEAMINASE DEFICIENT SEVERE COMBINED IMMUNE-DEFICIENCY AFTER TREATMENT WITH POLYETHYLENE-GLYCOL MODIFIED ADENOSINE-DEAMINASE |
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| Author(s): WEINBERG K, HERSHFIELD MS, BASTIAN J, KOHN D, SENDER L, PARKMAN R, LENARSKY C |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 92 Issue: 2 Pages: 596-602 Published: AUG 1993 |
| Times Cited: 38 References: 29 |
| Abstract: Adenosine deaminase (ADA) deficiency causes severe combined immune deficiency (SCID) by interfering with the metabolism of deoxyadenosine, which is toxic to T lymphocytes at all stages of differentiation. Enzyme replacement with polyethylene glycol-modified ADA (PEG-ADA) has been previously shown to correct deoxyadenosine metabolism and improve mitogen-induced T lymphocyte proliferation. We studied the biochemical and immunologic effects of PEG-ADA in two infants with ADA-deficient SCID. While in a catabolic state, higher doses of PEG-ADA than previously described were required to normalize deoxyadenosine metabolism. After biochemical improvement, the patients recovered immune function in a pattern similar to that observed in normal thymic ontogeny and in patients with immunological reconstitution after bone marrow transplantation. Immune reconstitution was marked by the sequential appearance in the peripheral blood of phenotypic T lymphocytes corresponding to successive stages of thymic differentiation. Functional reconstitution was marked by the successive appearance of mitogen responses dependent on exogenous in vitro IL-2, mitogen responses not requiring exogenous IL-2, antigen-specific responses dependent on exogenous IL-2, and finally, antigen-specific responses not requiring exogenous IL-2. Natural killer function was tested in one patient and normalized with PEG-ADA therapy. Optimal PEG-ADA therapy appears to normalize thymic differentiation in ADA-deficient SCID, resulting in normal antigen-specific immune function. |
| Document Type: Article |
| Language: English |
| Reprint Address: WEINBERG, K (reprint author), UNIV SO CALIF, CHILDRENS HOSP, SCH MED, DEPT PEDIAT, DIV RES IMMUNOL BONE MARROW TRANSPLANTAT, LOS ANGELES, CA 90027 USA |
Addresses:
1. CHILDRENS HOSP SAN DIEGO, SAN DIEGO, CA 92123 USA
2. DUKE UNIV, SCH MED, DEPT MED, DURHAM, NC 27710 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: LT169 |
| ISSN: 0021-9738 |
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