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T lymphocyte ontogeny in adenosine deaminase-deficient severe combined immune deficiency after treatment with polyethylene glycol-modified adenosine deaminase.

Publication ,  Journal Article
Weinberg, K; Hershfield, MS; Bastian, J; Kohn, D; Sender, L; Parkman, R; Lenarsky, C
Published in: J Clin Invest
August 1993

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.

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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

August 1993

Volume

92

Issue

2

Start / End Page

596 / 602

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • T-Lymphocytes
  • Severe Combined Immunodeficiency
  • Middle Aged
  • Lymphocyte Activation
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Killer Cells, Natural
  • Infant
  • Immunophenotyping
  • Immunology
 

Citation

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MLA
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Weinberg, K., Hershfield, M. S., Bastian, J., Kohn, D., Sender, L., Parkman, R., & Lenarsky, C. (1993). T lymphocyte ontogeny in adenosine deaminase-deficient severe combined immune deficiency after treatment with polyethylene glycol-modified adenosine deaminase. J Clin Invest, 92(2), 596–602. https://doi.org/10.1172/JCI116626
Weinberg, K., M. S. Hershfield, J. Bastian, D. Kohn, L. Sender, R. Parkman, and C. Lenarsky. “T lymphocyte ontogeny in adenosine deaminase-deficient severe combined immune deficiency after treatment with polyethylene glycol-modified adenosine deaminase.J Clin Invest 92, no. 2 (August 1993): 596–602. https://doi.org/10.1172/JCI116626.
Weinberg K, Hershfield MS, Bastian J, Kohn D, Sender L, Parkman R, et al. T lymphocyte ontogeny in adenosine deaminase-deficient severe combined immune deficiency after treatment with polyethylene glycol-modified adenosine deaminase. J Clin Invest. 1993 Aug;92(2):596–602.
Weinberg, K., et al. “T lymphocyte ontogeny in adenosine deaminase-deficient severe combined immune deficiency after treatment with polyethylene glycol-modified adenosine deaminase.J Clin Invest, vol. 92, no. 2, Aug. 1993, pp. 596–602. Pubmed, doi:10.1172/JCI116626.
Weinberg K, Hershfield MS, Bastian J, Kohn D, Sender L, Parkman R, Lenarsky C. T lymphocyte ontogeny in adenosine deaminase-deficient severe combined immune deficiency after treatment with polyethylene glycol-modified adenosine deaminase. J Clin Invest. 1993 Aug;92(2):596–602.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

August 1993

Volume

92

Issue

2

Start / End Page

596 / 602

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • T-Lymphocytes
  • Severe Combined Immunodeficiency
  • Middle Aged
  • Lymphocyte Activation
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Killer Cells, Natural
  • Infant
  • Immunophenotyping
  • Immunology