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Immunologic reconstitution during PEG-ADA therapy in an unusual mosaic ADA deficient patient.

Publication ,  Journal Article
Liu, P; Santisteban, I; Burroughs, LM; Ochs, HD; Torgerson, TR; Hershfield, MS; Rawlings, DJ; Scharenberg, AM
Published in: Clin Immunol
February 2009

We report detailed genetic and immunologic studies in a patient diagnosed with adenosine deaminase (ADA) deficiency and combined immune deficiency at age 5 years. At the time of diagnosis, although all other lymphocyte subsets were depleted, circulating CD8(+) T cells with a terminally differentiated phenotype were abundant and expressed normal ADA activity due to a reversion mutation in a CD8(+) T cell or precursor. Over the first 9 months of replacement therapy with PEG-ADA, the patient steadily accumulated mature naïve CD4(+) and CD8(+) T cells, as well as CD4(+)/FOXP3(+) regulatory T cells, consistent with restoration of a functional cellular immune system. While CD19(+) naïve B cells also accumulated in response to PEG-ADA therapy, a high proportion of these B cells exhibited an immature surface marker phenotype even after 9 months, and immunization with neoantigen bacteriophage varphiX174 demonstrated a markedly subnormal humoral immune response. Our observations in this single patient have important implications for gene therapy of human ADA deficiency, as they indicate that ADA expression within even a large circulating lymphocyte population may not be sufficient to support adequate immune reconstitution. They also suggest that an immature surface marker phenotype of the peripheral B cell compartment may be a useful surrogate marker for incomplete humoral immune reconstitution during enzyme replacement, and possibly other forms of hematopoietic cell therapies.

Duke Scholars

Published In

Clin Immunol

DOI

EISSN

1521-7035

Publication Date

February 2009

Volume

130

Issue

2

Start / End Page

162 / 174

Location

United States

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • Severe Combined Immunodeficiency
  • Male
  • Immunology
  • Humans
  • Child, Preschool
  • CD8-Positive T-Lymphocytes
  • CD4-Positive T-Lymphocytes
  • Bacteriophage phi X 174
  • B-Lymphocyte Subsets
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Liu, P., Santisteban, I., Burroughs, L. M., Ochs, H. D., Torgerson, T. R., Hershfield, M. S., … Scharenberg, A. M. (2009). Immunologic reconstitution during PEG-ADA therapy in an unusual mosaic ADA deficient patient. Clin Immunol, 130(2), 162–174. https://doi.org/10.1016/j.clim.2008.08.026
Liu, Ping, Ines Santisteban, Lauri M. Burroughs, Hans D. Ochs, Troy R. Torgerson, Michael S. Hershfield, David J. Rawlings, and Andrew M. Scharenberg. “Immunologic reconstitution during PEG-ADA therapy in an unusual mosaic ADA deficient patient.Clin Immunol 130, no. 2 (February 2009): 162–74. https://doi.org/10.1016/j.clim.2008.08.026.
Liu P, Santisteban I, Burroughs LM, Ochs HD, Torgerson TR, Hershfield MS, et al. Immunologic reconstitution during PEG-ADA therapy in an unusual mosaic ADA deficient patient. Clin Immunol. 2009 Feb;130(2):162–74.
Liu, Ping, et al. “Immunologic reconstitution during PEG-ADA therapy in an unusual mosaic ADA deficient patient.Clin Immunol, vol. 130, no. 2, Feb. 2009, pp. 162–74. Pubmed, doi:10.1016/j.clim.2008.08.026.
Liu P, Santisteban I, Burroughs LM, Ochs HD, Torgerson TR, Hershfield MS, Rawlings DJ, Scharenberg AM. Immunologic reconstitution during PEG-ADA therapy in an unusual mosaic ADA deficient patient. Clin Immunol. 2009 Feb;130(2):162–174.
Journal cover image

Published In

Clin Immunol

DOI

EISSN

1521-7035

Publication Date

February 2009

Volume

130

Issue

2

Start / End Page

162 / 174

Location

United States

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • Severe Combined Immunodeficiency
  • Male
  • Immunology
  • Humans
  • Child, Preschool
  • CD8-Positive T-Lymphocytes
  • CD4-Positive T-Lymphocytes
  • Bacteriophage phi X 174
  • B-Lymphocyte Subsets