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Somatic mosaicism caused by monoallelic reversion of a mutation in T cells of a patient with ADA-SCID and the effects of enzyme replacement therapy on the revertant phenotype.

Publication ,  Journal Article
Moncada-Vélez, M; Vélez-Ortega, A; Orrego, J; Santisteban, I; Jagadeesh, J; Olivares, M; Olaya, N; Hershfield, M; Candotti, F; Franco, J
Published in: Scand J Immunol
November 2011

Patients with adenosine deaminase (ADA) deficiency exhibit spontaneous and partial clinical remission associated with somatic reversion of inherited mutations. We report a child with severe combined immunodeficiency (T-B- SCID) due to ADA deficiency diagnosed at the age of 1 month, whose lymphocyte counts including CD4+ and CD8+ T and NK cells began to improve after several months with normalization of ADA activity in Peripheral blood lymphocytes (PBL), as a result of somatic mosaicism caused by monoallelic reversion of the causative mutation in the ADA gene. He was not eligible for haematopoietic stem cell transplantation (HSCT) or gene therapy (GT); therefore he was placed on enzyme replacement therapy (ERT) with bovine PEG-ADA. The follow-up of metabolic and immunologic responses to ERT included gradual improvement in ADA activity in erythrocytes and transient expansion of most lymphocyte subsets, followed by gradual stabilization of CD4+ and CD8+ T (with naïve phenotype) and NK cells, and sustained expansion of TCRγδ+ T cells. This was accompanied by the disappearance of the revertant T cells as shown by DNA sequencing from PBL. Although the patient's clinical condition improved marginally, he later developed a germinal cell tumour and eventually died at the age of 67 months from sepsis. This case adds to our current knowledge of spontaneous reversion of mutations in ADA deficiency and shows that the effects of the ERT may vary among these patients, suggesting that it could depend on the cell and type in which the somatic mosaicism is established upon reversion.

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Published In

Scand J Immunol

DOI

EISSN

1365-3083

Publication Date

November 2011

Volume

74

Issue

5

Start / End Page

471 / 481

Location

England

Related Subject Headings

  • Shock, Septic
  • Severe Combined Immunodeficiency
  • Receptors, Antigen, T-Cell
  • Neoplasms, Unknown Primary
  • Mutation
  • Mosaicism
  • Male
  • Lung Neoplasms
  • Killer Cells, Natural
  • Infant
 

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Moncada-Vélez, M., Vélez-Ortega, A., Orrego, J., Santisteban, I., Jagadeesh, J., Olivares, M., … Franco, J. (2011). Somatic mosaicism caused by monoallelic reversion of a mutation in T cells of a patient with ADA-SCID and the effects of enzyme replacement therapy on the revertant phenotype. Scand J Immunol, 74(5), 471–481. https://doi.org/10.1111/j.1365-3083.2011.02593.x
Moncada-Vélez, M., A. Vélez-Ortega, J. Orrego, I. Santisteban, J. Jagadeesh, M. Olivares, N. Olaya, M. Hershfield, F. Candotti, and J. Franco. “Somatic mosaicism caused by monoallelic reversion of a mutation in T cells of a patient with ADA-SCID and the effects of enzyme replacement therapy on the revertant phenotype.Scand J Immunol 74, no. 5 (November 2011): 471–81. https://doi.org/10.1111/j.1365-3083.2011.02593.x.
Moncada-Vélez M, Vélez-Ortega A, Orrego J, Santisteban I, Jagadeesh J, Olivares M, et al. Somatic mosaicism caused by monoallelic reversion of a mutation in T cells of a patient with ADA-SCID and the effects of enzyme replacement therapy on the revertant phenotype. Scand J Immunol. 2011 Nov;74(5):471–81.
Moncada-Vélez, M., et al. “Somatic mosaicism caused by monoallelic reversion of a mutation in T cells of a patient with ADA-SCID and the effects of enzyme replacement therapy on the revertant phenotype.Scand J Immunol, vol. 74, no. 5, Nov. 2011, pp. 471–81. Pubmed, doi:10.1111/j.1365-3083.2011.02593.x.
Moncada-Vélez M, Vélez-Ortega A, Orrego J, Santisteban I, Jagadeesh J, Olivares M, Olaya N, Hershfield M, Candotti F, Franco J. Somatic mosaicism caused by monoallelic reversion of a mutation in T cells of a patient with ADA-SCID and the effects of enzyme replacement therapy on the revertant phenotype. Scand J Immunol. 2011 Nov;74(5):471–481.
Journal cover image

Published In

Scand J Immunol

DOI

EISSN

1365-3083

Publication Date

November 2011

Volume

74

Issue

5

Start / End Page

471 / 481

Location

England

Related Subject Headings

  • Shock, Septic
  • Severe Combined Immunodeficiency
  • Receptors, Antigen, T-Cell
  • Neoplasms, Unknown Primary
  • Mutation
  • Mosaicism
  • Male
  • Lung Neoplasms
  • Killer Cells, Natural
  • Infant