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IgG antibody response to polyethylene glycol-modified adenosine deaminase in patients with adenosine deaminase deficiency.

Publication ,  Journal Article
Chaffee, S; Mary, A; Stiehm, ER; Girault, D; Fischer, A; Hershfield, MS
Published in: J Clin Invest
May 1992

Polyethylene glycol (PEG)-modified bovine adenosine deaminase (ADA) is used for replacement therapy of severe combined immunodeficiency disease due to inherited ADA deficiency. We monitored IgG anti-ADA antibody in 17 patients treated by intramuscular injections of PEG-ADA for 1 to greater than 5.5 yr. ELISA-detectable anti-ADA IgG appeared in 10 patients, usually between the third and eighth months of treatment. Anti-ADA levels did not correlate with trough plasma ADA activity, which averaged 1.8-5 times normal blood (erythrocyte) ADA activity, depending on dose (15-60 U/kg per wk). ELISA-detectable anti-ADA antibodies were directed primarily at bovine-specific peptide (rather than PEG-containing) epitopes. Enhanced enzyme clearance, mediated by antibody that directly inhibited native and PEG-modified bovine ADA, and native, but not PEG-modified human ADA, occurred in two patients. In one, tolerance was induced; in the second, twice weekly injections of PEG-ADA compensated for accelerated clearance. We speculate that inhibitory antibodies recognize conserved, relatively PEG-free epitope(s) encompassing the active site, and that in human, but not bovine, ADA a PEG-attachment site "shields" the active site from immune recognition. We conclude that PEG-modification largely prevents the development of high affinity, or high levels of clearing antibodies to bovine ADA, and that PEG-modified human ADA should be further investigated as a possible treatment for ADA deficiency.

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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

May 1992

Volume

89

Issue

5

Start / End Page

1643 / 1651

Location

United States

Related Subject Headings

  • Species Specificity
  • Polyethylene Glycols
  • Infant
  • Immunology
  • Immunoglobulin G
  • Humans
  • Child, Preschool
  • Child
  • Cattle
  • Autoantibodies
 

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Chaffee, S., Mary, A., Stiehm, E. R., Girault, D., Fischer, A., & Hershfield, M. S. (1992). IgG antibody response to polyethylene glycol-modified adenosine deaminase in patients with adenosine deaminase deficiency. J Clin Invest, 89(5), 1643–1651. https://doi.org/10.1172/JCI115761
Chaffee, S., A. Mary, E. R. Stiehm, D. Girault, A. Fischer, and M. S. Hershfield. “IgG antibody response to polyethylene glycol-modified adenosine deaminase in patients with adenosine deaminase deficiency.J Clin Invest 89, no. 5 (May 1992): 1643–51. https://doi.org/10.1172/JCI115761.
Chaffee S, Mary A, Stiehm ER, Girault D, Fischer A, Hershfield MS. IgG antibody response to polyethylene glycol-modified adenosine deaminase in patients with adenosine deaminase deficiency. J Clin Invest. 1992 May;89(5):1643–51.
Chaffee, S., et al. “IgG antibody response to polyethylene glycol-modified adenosine deaminase in patients with adenosine deaminase deficiency.J Clin Invest, vol. 89, no. 5, May 1992, pp. 1643–51. Pubmed, doi:10.1172/JCI115761.
Chaffee S, Mary A, Stiehm ER, Girault D, Fischer A, Hershfield MS. IgG antibody response to polyethylene glycol-modified adenosine deaminase in patients with adenosine deaminase deficiency. J Clin Invest. 1992 May;89(5):1643–1651.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

May 1992

Volume

89

Issue

5

Start / End Page

1643 / 1651

Location

United States

Related Subject Headings

  • Species Specificity
  • Polyethylene Glycols
  • Infant
  • Immunology
  • Immunoglobulin G
  • Humans
  • Child, Preschool
  • Child
  • Cattle
  • Autoantibodies