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A novel immunodeficiency associated with hypomorphic RAG1 mutations and CMV infection
Jean-Pierre de Villartay, … , Alain Fischer, Françoise Le Deist
Jean-Pierre de Villartay, … , Alain Fischer, Françoise Le Deist
Published November 1, 2005
Citation Information: J Clin Invest. 2005;115(11):3291-3299. https://doi.org/10.1172/JCI25178.
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Research Article Aging

A novel immunodeficiency associated with hypomorphic RAG1 mutations and CMV infection

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Abstract

Amorphic mutations in the recombination activating genes RAG1 and RAG2 have been reported to cause T–B– SCID, whereas hypomorphic mutations led to the expansion of a few autoimmune T cell clones responsible for the Omenn syndrome phenotype. We report here a novel clinical and immunological phenotype associated with recessive RAG1 hypomorphic mutations in 4 patients from 4 different families. The immunological phenotype consists of the oligoclonal expansion of TCRγδ T cells combined with TCRαβ T cell lymphopenia. The clinical phenotype consists of severe, disseminated CMV infection and autoimmune blood cell manifestations. Repertoire studies suggest that CMV infection, in the setting of this particular T cell immunodeficiency, may have driven the TCRγδ T cell clonal expansion. This observation extends the range of clinical and immunological phenotypes associated with RAG mutations, emphasizing the role of the genetic background and microbial environment in determining disease phenotype.

Authors

Jean-Pierre de Villartay, Annick Lim, Hamoud Al-Mousa, Sophie Dupont, Julie Déchanet-Merville, Edith Coumau-Gatbois, Marie-Lise Gougeon, Arnaud Lemainque, Céline Eidenschenk, Emmanuelle Jouanguy, Laurent Abel, Jean-Laurent Casanova, Alain Fischer, Françoise Le Deist

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Figure 1

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TCRVB usage by patients’ T lymphocytes. (A) VB repertoire was determined...
TCRVB usage by patients’ T lymphocytes. (A) VB repertoire was determined either using available specific mAb in immunofluorescence assay in P2 and P4 or using real-time PCR analysis assay in P3. In this latter patient, similar results were obtained by PCR analysis and using available specific mAb in immunofluorescence assay (data not shown). The x axis indicates VB families; the y axis indicates relative frequency of usage (%) within the TCRαβ T cells. Controls values shown in rectangles represent mean ± 2 SDs. Gray bars indicate abnormal VB usage. *Not done. (B) Profiles of the fluorescent Vβ-Cβ runoff products obtained with mononuclear cells. The x axis indicates CDR3 length.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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