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Molecular basis for paradoxical carriers of adenosine deaminase (ADA) deficiency that show extremely low levels of ADA activity in peripheral blood cells without immunodeficiency.

Publication ,  Journal Article
Ariga, T; Oda, N; Sanstisteban, I; Arredondo-Vega, FX; Shioda, M; Ueno, H; Terada, K; Kobayashi, K; Hershfield, MS; Sakiyama, Y
Published in: J Immunol
February 1, 2001

Adenosine deaminase (ADA) deficiency causes an autosomal recessive form of severe combined immunodeficiency and also less severe phenotypes, depending to a large degree on genotype. In general, ADA activity in cells of carriers is approximately half-normal. Unexpectedly, healthy first-degree relatives of two unrelated ADA-deficient severe combined immunodeficient patients (mother and brother in family I; mother in family II) had only 1-2% of normal ADA activity in PBMC, lower than has previously been found in PBMC of healthy individuals with so-called "partial ADA deficiency." The level of deoxyadenosine nucleotides in erythrocytes of these paradoxical carriers was slightly elevated, but much lower than levels found in immunodeficient patients with ADA deficiency. ADA activity in EBV-lymphoblastoid cell lines (LCL) and T cell lines established from these carriers was 10-20% of normal. Each of these carriers possessed two mutated ADA alleles. Expression of cloned mutant ADA cDNAs in an ADA-deletion strain of Escherichia coli indicated that the novel mutations G239S and M310T were responsible for the residual ADA activity. ADA activity in EBV-LCL extracts of the paradoxical carriers was much more labile than ADA from normal EBV-LCL. Immunoblotting suggested that this lability was due to denaturation rather than to degradation of the mutant protein. These results further define the threshold level of ADA activity necessary for sustaining immune function.

Duke Scholars

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

February 1, 2001

Volume

166

Issue

3

Start / End Page

1698 / 1702

Location

United States

Related Subject Headings

  • Severe Combined Immunodeficiency
  • Pedigree
  • Mutation, Missense
  • Male
  • Infant
  • Immunology
  • Humans
  • Hot Temperature
  • Genetic Carrier Screening
  • Gene Expression Profiling
 

Citation

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Ariga, T., Oda, N., Sanstisteban, I., Arredondo-Vega, F. X., Shioda, M., Ueno, H., … Sakiyama, Y. (2001). Molecular basis for paradoxical carriers of adenosine deaminase (ADA) deficiency that show extremely low levels of ADA activity in peripheral blood cells without immunodeficiency. J Immunol, 166(3), 1698–1702. https://doi.org/10.4049/jimmunol.166.3.1698
Ariga, T., N. Oda, I. Sanstisteban, F. X. Arredondo-Vega, M. Shioda, H. Ueno, K. Terada, K. Kobayashi, M. S. Hershfield, and Y. Sakiyama. “Molecular basis for paradoxical carriers of adenosine deaminase (ADA) deficiency that show extremely low levels of ADA activity in peripheral blood cells without immunodeficiency.J Immunol 166, no. 3 (February 1, 2001): 1698–1702. https://doi.org/10.4049/jimmunol.166.3.1698.
Ariga, T., et al. “Molecular basis for paradoxical carriers of adenosine deaminase (ADA) deficiency that show extremely low levels of ADA activity in peripheral blood cells without immunodeficiency.J Immunol, vol. 166, no. 3, Feb. 2001, pp. 1698–702. Pubmed, doi:10.4049/jimmunol.166.3.1698.
Ariga T, Oda N, Sanstisteban I, Arredondo-Vega FX, Shioda M, Ueno H, Terada K, Kobayashi K, Hershfield MS, Sakiyama Y. Molecular basis for paradoxical carriers of adenosine deaminase (ADA) deficiency that show extremely low levels of ADA activity in peripheral blood cells without immunodeficiency. J Immunol. 2001 Feb 1;166(3):1698–1702.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

February 1, 2001

Volume

166

Issue

3

Start / End Page

1698 / 1702

Location

United States

Related Subject Headings

  • Severe Combined Immunodeficiency
  • Pedigree
  • Mutation, Missense
  • Male
  • Infant
  • Immunology
  • Humans
  • Hot Temperature
  • Genetic Carrier Screening
  • Gene Expression Profiling