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Normal IgH Repertoire Diversity in an Infant with ADA Deficiency After Gene Therapy.

Publication ,  Journal Article
Baloh, CH; Borkar, SA; Chang, K-F; Yao, J; Hershfield, MS; Parikh, SH; Kohn, DB; Goodenow, MM; Sleasman, JW; Yin, L
Published in: J Clin Immunol
October 2021

PURPOSE: Adenosine deaminase (ADA) deficiency causes severe combined immunodeficiency (SCID) through an accumulation of toxic metabolites within lymphocytes. Recently, ADA deficiency has been successfully treated using lentiviral-transduced autologous CD34+ cells carrying the ADA gene. T and B cell function appears to be fully restored, but in many patients' B cell numbers remain low, and assessments of the immunoglobulin heavy (IgHV) repertoire following gene therapy are lacking. METHODS: We performed deep sequencing of IgHV repertoire in peripheral blood lymphocytes from a child following lentivirus-based gene therapy for ADA deficiency and compared to the IgHV repertoire in healthy infants and adults. RESULTS: After gene therapy, Ig diversity increased over time as evidenced by V, D, and J gene usage, N-additions, CDR3 length, extent of somatic hypermutation, and Ig class switching. There was the emergence of predominant IgHM, IgHG, and IgHA CDR3 lengths after gene therapy indicating successful oligoclonal expansion in response to antigens. This provides proof of concept for the feasibility and utility of molecular monitoring in following B cell reconstitution following gene therapy for ADA deficiency. CONCLUSION: Based on deep sequencing, gene therapy resulted in an IgHV repertoire with molecular diversity similar to healthy infants.

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Published In

J Clin Immunol

DOI

EISSN

1573-2592

Publication Date

October 2021

Volume

41

Issue

7

Start / End Page

1597 / 1606

Location

Netherlands

Related Subject Headings

  • Severe Combined Immunodeficiency
  • Lymphocyte Count
  • Infant
  • Immunology
  • Immunoglobulin Heavy Chains
  • Humans
  • Genetic Therapy
  • Female
  • Enzyme Replacement Therapy
  • Agammaglobulinemia
 

Citation

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Baloh, C. H., Borkar, S. A., Chang, K.-F., Yao, J., Hershfield, M. S., Parikh, S. H., … Yin, L. (2021). Normal IgH Repertoire Diversity in an Infant with ADA Deficiency After Gene Therapy. J Clin Immunol, 41(7), 1597–1606. https://doi.org/10.1007/s10875-021-01034-2
Baloh, Carolyn H., Samiksha A. Borkar, Kai-Fen Chang, Jiqiang Yao, Michael S. Hershfield, Suhag H. Parikh, Donald B. Kohn, Maureen M. Goodenow, John W. Sleasman, and Li Yin. “Normal IgH Repertoire Diversity in an Infant with ADA Deficiency After Gene Therapy.J Clin Immunol 41, no. 7 (October 2021): 1597–1606. https://doi.org/10.1007/s10875-021-01034-2.
Baloh CH, Borkar SA, Chang K-F, Yao J, Hershfield MS, Parikh SH, et al. Normal IgH Repertoire Diversity in an Infant with ADA Deficiency After Gene Therapy. J Clin Immunol. 2021 Oct;41(7):1597–606.
Baloh, Carolyn H., et al. “Normal IgH Repertoire Diversity in an Infant with ADA Deficiency After Gene Therapy.J Clin Immunol, vol. 41, no. 7, Oct. 2021, pp. 1597–606. Pubmed, doi:10.1007/s10875-021-01034-2.
Baloh CH, Borkar SA, Chang K-F, Yao J, Hershfield MS, Parikh SH, Kohn DB, Goodenow MM, Sleasman JW, Yin L. Normal IgH Repertoire Diversity in an Infant with ADA Deficiency After Gene Therapy. J Clin Immunol. 2021 Oct;41(7):1597–1606.
Journal cover image

Published In

J Clin Immunol

DOI

EISSN

1573-2592

Publication Date

October 2021

Volume

41

Issue

7

Start / End Page

1597 / 1606

Location

Netherlands

Related Subject Headings

  • Severe Combined Immunodeficiency
  • Lymphocyte Count
  • Infant
  • Immunology
  • Immunoglobulin Heavy Chains
  • Humans
  • Genetic Therapy
  • Female
  • Enzyme Replacement Therapy
  • Agammaglobulinemia