Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis
Despina Moshous, … , Jean-Laurent Casanova, Jean-Pierre de Villartay
Despina Moshous, … , Jean-Laurent Casanova, Jean-Pierre de Villartay
Published February 1, 2003
Citation Information: J Clin Invest. 2003;111(3):381-387. https://doi.org/10.1172/JCI16774.
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Article Immunology

Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis

Abstract

We have previously described the identification of Artemis, a factor involved in the nonhomologous end joining (NHEJ) phase of V(D)J recombination of T and B cell receptor genes. Null mutations of the Artemis gene result in a complete absence of T and B lymphocytes that is associated with increased cell radiosensitivity, causing the radiosensitive T–B– SCID (RS-SCID) condition. We presently report the occurrence of hypomorphic mutations of the Artemis gene in four patients from two kindreds. Partially preserved in vivo activity of Artemis is associated with the presence of polyclonal T and B lymphocyte populations, albeit in reduced numbers, along with chromosomal instability and development of EBV-associated lymphoma in two of four patients. This syndrome emphasizes the role of Artemis in the NHEJ pathway of DNA repair and suggests that other, yet ill-defined, conditions associating immunodeficiency and lymphoma could be caused by mutations in genes encoding NHEJ factors.

Authors

Despina Moshous, Christophe Pannetier, Régina de Chasseval, Françoise le Deist, Marina Cavazzana-Calvo, Serge Romana, Elizabeth Macintyre, Danielle Canioni, Nicole Brousse, Alain Fischer, Jean-Laurent Casanova, Jean-Pierre de Villartay

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Complementation of IR sensitivity. (a) Fibroblasts from P70 were complem...
Complementation of IR sensitivity. (a) Fibroblasts from P70 were complemented with WT Artemis. The selective advantage of transduced cells after 3 Gy IR was assessed over time. The control curves, (vector 0 Gy) and (vector 3 Gy), are superimposed. (b) Fibroblasts from an Artemis-deficient patient were complemented with either the WT or the P70-specific truncated form of Artemis. The selective advantage of transduced cells after 4 Gy IR was assessed over time. Results are expressed as the GFP+/GFP– cell ratio over time following irradiation.