HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ariga, T. Articles by Sakiyama, Y. Search for Related Content PubMed PubMed Citation Articles by Ariga, T. Articles by 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 Immunodeficiency¹

Tadashi Ariga^2,*, Noriko Oda^*, Ines Sanstisteban, Francisco X. Arredondo-Vega, Mitsutaka Shioda, Hideki Ueno, Kihei Terada^¶, Kunihiko Kobayashi, Michael S. Hershfield and Yukio Sakiyama^*

^* Department of Human Gene Therapy and Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan; Department of Medicine and Biochemistry, Duke University Medical Center, Durham, NC 27710; Department of Pediatrics, Matsue Red Cross Hospital, Matsue, Japan; and ^¶ Department of Pediatrics, Kawasaki Medical School, Kurashiki, Japan

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.

This article has been cited by other articles:

				F. Carlucci, A. Tabucchi, A. Aiuti, F. Rosi, F. Floccari, R. Pagani, and E. Marinello Capillary Electrophoresis in Diagnosis and Monitoring of Adenosine Deaminase Deficiency Clin. Chem., November 1, 2003; 49(11): 1830 - 1838. [Abstract] [Full Text] [PDF]

				F. X. Arredondo-Vega, I. Santisteban, E. Richard, P. Bali, M. Koleilat, M. Loubser, A. Al-Ghonaium, M. Al-Helali, and M. S. Hershfield Adenosine deaminase deficiency with mosaicism for a "second-site suppressor" of a splicing mutation: decline in revertant T lymphocytes during enzyme replacement therapy Blood, February 1, 2002; 99(3): 1005 - 1013. [Abstract] [Full Text] [PDF]

				T. Ariga, N. Oda, K. Yamaguchi, N. Kawamura, H. Kikuta, S. Taniuchi, Y. Kobayashi, K. Terada, H. Ikeda, M. S. Hershfield, et al. T-cell lines from 2 patients with adenosine deaminase (ADA) deficiency showed the restoration of ADA activity resulted from the reversion of an inherited mutation Blood, May 1, 2001; 97(9): 2896 - 2899. [Abstract] [Full Text] [PDF]