Inproceedings: an article in a conference proceedings.
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Somatic reversion in a patient with X-linked SCID: a limited cure?
Title of the conference
13th Meeting of the European Society for Immunology
sHertogenbosch, Netherlands, October 16-19, 2008
Clinical and Experimental Immunology
Severe combined immunodeficiency (SCID) is a lifethreateningdisorder caused by mutations in several genesinvolved in lymphocyte development. However, somemutations in the same genes can also result in muchmilder phenotypes, often with features of immunedysregulation rather than profound susceptibility toinfections. We describe a 5-year-old boy who initiallypresented with a self-limiting granulomatous skin disorderand prolonged infection-associated neutropenia.Persisting moderate lymphopenia prompted furtherimmunological investigations. He had 500 T cells, 700 Bcells and 10 NK cells with < 10% naı¨ve CD4 cells and apredominance of gamma/delta T cells (50%). Low T andNK cells with normal B cells in a male patient suggested adefect in IL2R gamma chain and indeed a novel T466Cpoint mutation was confirmed by genomic sequencing.Interestingly, the mutation was found in B, NK andbuccal epithelial cells, while alpha/beta and gamma/deltaT cells showed a normal sequence, suggesting in vivoreversion on the level of a T-cell committed progenitor.Genetic correction of the defect in T cells led to (i)generation of a diverse, but skewed T cell receptorrepertoire; (ii) T cells with impaired proliferativeresponses; (iii) subnormal total IgG production with nospecific antibodies; but (iv) significant clinical immunitypotentially associated with the compensatory increase ingamma/delta T cells. This second patient with somaticreversion in IL2R gamma chain illustrates the developmentalpotential of single revertant progenitors. However,limited functional correction and the progressiveimmunodeficiency leading to subsequent stem cell transplantationin the first patient also demonstrates the needfor careful follow-up of these patients.
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