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.
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
Title and authors | Publication | Year |
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Broad Spectrum Antibodies to Self-Antigens and Cytokines in RAG Deficiency
Jolan Walter, Lindsey B. Rosen, Krisztian Csomos, Jacob Rosenberg, Divij Mathew, Marton Keszei, Boglarka Ujhazi, Karin Chen, Yu Nee Lee, Irit Tirosh, Kerry Dobbs, Waleed Al-Herz, Morton Cowan, Jennifer Puck, Jack J. Bleesing, Michael S. Grimley, Harry L. Malech, Suk See De Ravin, Andrew R. Gennery, Roshini S. Abraham, Avni Y. Joshi, Thomas G. Boyce, Manish Butte, Kari Christine Nadeau, Imelda Balboni, Kathleen Sullivan, Javeed Akhter, Mehdi Adeli, Reem A. Elfeky, Dalia H. El-Ghoneimy, Ghassan Dbaibo, Rima Wakim, Chiara Azzari, PAOLO PALMA, caterina cancrini, Kelly Capuder, Antonio Condino-Neto, Beatriz T. Costa-Carvalho, Joao Bosco Oliveira, Chaim M Roifman, David Buchbinder, Attila Kumanovics, Jose Franco, Tim Niehues, Catharina Schuetz, Taco Kuijpers, Christina Yee, Janet Chou, Michel Massaad, Raif Geha, Gulbu Uzel, Rebecca Gelman, Steven M. Holland, Mike Recher, Paul J. Utz, Sarah K Browne, Luigi Daniele Notarangelo |
Journal of Clinical Investigation | 2015 |
Direct and Indirect Effects of Cytomegalovirus-Induced γδ T Cells after Kidney Transplantation
L Couzi, V Pitard, JF Moreau, P Merville, J Déchanet-Merville |
Frontiers in immunology | 2015 |
RAG1 Deficiency May Present Clinically as Selective IgA Deficiency
T Kato, E Crestani, C Kamae, K Honma, T Yokosuka, T Ikegawa, N Nishida, H Kanegane, T Wada, A Yachie, O Ohara, T Morio, LD Notarangelo, K Imai, S Nonoyama |
Journal of Clinical Immunology | 2015 |
Compound Heterozygous Mutation of Rag1 Leading to Omenn Syndrome
AG Matthews, CE Briggs, K Yamanaka, TN Small, JL Mooster, FA Bonilla, MA Oettinger, MJ Butte, SD Fugmann |
PloS one | 2015 |
Leaky RAG Deficiency in Adult Patients with Impaired Antibody Production against Bacterial Polysaccharide Antigens
CB Geier, A Piller, A Linder, KM Sauerwein, MM Eibl, HM Wolf, F Rieux-Laucat |
PloS one | 2015 |
Primary immunodeficiency update
DC Pichard, AF Freeman, EW Cowen |
Journal of the American Academy of Dermatology | 2015 |
Late-Onset Combined Immunodeficiency with a Novel IL2RG Mutation and Probable Revertant Somatic Mosaicism
Y Okuno, A Hoshino, H Muramatsu, N Kawashima, X Wang, K Yoshida, T Wada, M Gunji, T Toma, T Kato, Y Shiraishi, A Iwata, T Hori, T Kitoh, K Chiba, H Tanaka, M Sanada, Y Takahashi, S Nonoyama, M Ito, S Miyano, S Ogawa, S Kojima, H Kanegane |
Journal of Clinical Immunology | 2015 |
Late Onset Hypomorphic RAG2 Deficiency Presentation with Fatal Vaccine-Strain VZV Infection
CM Dutmer, EJ Asturias, C Smith, MK Dishop, DS Schmid, WJ Bellini, I Tirosh, YN Lee, LD Notarangelo, EW Gelfand |
Journal of Clinical Immunology | 2015 |
Molecular Characteristics, Clinical and Immunologic Manifestations of 11 Children with Omenn Syndrome in East Slavs (Russia, Belarus, Ukraine)
SO Sharapova, IE Guryanova, OE Pashchenko, IV Kondratenko, LV Kostyuchenko, YA Rodina, TV Varlamova, AV Bondarenko, LI Chernyshova, MN Gyseva, MV Belevtsev, NV Minakovskaya, OV Aleinikova |
Journal of Clinical Immunology | 2015 |