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Reduced thymic output, increased spontaneous apoptosis and oligoclonal B cells in polyethylene glycol-adenosine deaminase-treated patients.

Publication ,  Journal Article
Malacarne, F; Benicchi, T; Notarangelo, LD; Mori, L; Parolini, S; Caimi, L; Hershfield, M; Notarangelo, LD; Imberti, L
Published in: Eur J Immunol
November 2005

Impairment of purine metabolism due to adenosine deaminase (ADA) deficiency is associated with a severe combined immunodeficiency (SCID). Polyethylene glycol-modified ADA (PEG-ADA) has provided noncurative, life-saving treatment for these patients, but full immune recovery is not achieved with this therapy. Since ADA-SCID is perhaps the most difficult form of SCID to handle clinically, understanding the benefits and limitations of PEG-ADA therapy may be relevant for treatment selection. To this purpose, we analyzed the rate of thymic output, T and B cell repertoires, number of T cell divisions, IFN-gamma and IL-4 production, and the extent of cell death in five ADA-SCID patients following a prolonged period of treatment with PEG-ADA. We found that thymic output was low in these patients. However, their T cell repertoire was heterogeneous, and their T lymphocytes produced cytokines upon activation and responded to mitogen stimulation, although with different kinetics. Furthermore, a high number of peripheral T lymphocytes were committed to apoptosis. Anomalies were also observed in the B cell compartment, with oligoclonal expansions of B cell clonotypes in two patients. Our data indicate that decreased thymic function, B cell oligoclonality, and increased spontaneous apoptosis may be the mechanisms by which the immunodeficiency of ADA-SCID patients persists in spite of treatment with PEG-ADA.

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Published In

Eur J Immunol

DOI

ISSN

0014-2980

Publication Date

November 2005

Volume

35

Issue

11

Start / End Page

3376 / 3386

Location

Germany

Related Subject Headings

  • Thymus Gland
  • T-Lymphocytes
  • Severe Combined Immunodeficiency
  • Molecular Sequence Data
  • Male
  • Lymphopenia
  • Immunophenotyping
  • Immunology
  • Immunoglobulin Heavy Chains
  • Humans
 

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Malacarne, F., Benicchi, T., Notarangelo, L. D., Mori, L., Parolini, S., Caimi, L., … Imberti, L. (2005). Reduced thymic output, increased spontaneous apoptosis and oligoclonal B cells in polyethylene glycol-adenosine deaminase-treated patients. Eur J Immunol, 35(11), 3376–3386. https://doi.org/10.1002/eji.200526248
Malacarne, Fabio, Tiziana Benicchi, Lucia Dora Notarangelo, Luigi Mori, Silvia Parolini, Luigi Caimi, Michael Hershfield, Luigi Daniele Notarangelo, and Luisa Imberti. “Reduced thymic output, increased spontaneous apoptosis and oligoclonal B cells in polyethylene glycol-adenosine deaminase-treated patients.Eur J Immunol 35, no. 11 (November 2005): 3376–86. https://doi.org/10.1002/eji.200526248.
Malacarne F, Benicchi T, Notarangelo LD, Mori L, Parolini S, Caimi L, et al. Reduced thymic output, increased spontaneous apoptosis and oligoclonal B cells in polyethylene glycol-adenosine deaminase-treated patients. Eur J Immunol. 2005 Nov;35(11):3376–86.
Malacarne, Fabio, et al. “Reduced thymic output, increased spontaneous apoptosis and oligoclonal B cells in polyethylene glycol-adenosine deaminase-treated patients.Eur J Immunol, vol. 35, no. 11, Nov. 2005, pp. 3376–86. Pubmed, doi:10.1002/eji.200526248.
Malacarne F, Benicchi T, Notarangelo LD, Mori L, Parolini S, Caimi L, Hershfield M, Imberti L. Reduced thymic output, increased spontaneous apoptosis and oligoclonal B cells in polyethylene glycol-adenosine deaminase-treated patients. Eur J Immunol. 2005 Nov;35(11):3376–3386.
Journal cover image

Published In

Eur J Immunol

DOI

ISSN

0014-2980

Publication Date

November 2005

Volume

35

Issue

11

Start / End Page

3376 / 3386

Location

Germany

Related Subject Headings

  • Thymus Gland
  • T-Lymphocytes
  • Severe Combined Immunodeficiency
  • Molecular Sequence Data
  • Male
  • Lymphopenia
  • Immunophenotyping
  • Immunology
  • Immunoglobulin Heavy Chains
  • Humans