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Journal of Clinical Immunology

, Volume 32, Issue 4, pp 690–697 | Cite as

Multiple Reversions of an IL2RG Mutation Restore T cell Function in an X-linked Severe Combined Immunodeficiency Patient

  • Tomoki Kawai
  • Megumu Saito
  • Ryuta NishikomoriEmail author
  • Takahiro Yasumi
  • Kazushi Izawa
  • Tomohiko Murakami
  • Shigefumi Okamoto
  • Yasuko Mori
  • Noriko Nakagawa
  • Kohsuke Imai
  • Shigeaki Nonoyama
  • Taizo Wada
  • Akihiro Yachie
  • Katsuyuki Ohmori
  • Tatsutoshi Nakahata
  • Toshio Heike
Article

Abstract

Reversion mosaicism is increasingly being reported in primary immunodeficiency diseases, but there have been few cases with clinically improved immune function. Here, a case is reported of X-linked severe combined immunodeficiency (SCID-X1) with multiple somatic reversions in T cells, which restored sufficient cell-mediated immunity to overcome viral infection. Lineage-specific analysis revealed multiple reversions in T cell receptor (TCR) αβ+ and TCRγδ+ T cells. Diversity of the TCRVβ repertoire was comparable to normal and, furthermore, mitogen-induced proliferation of the patient’s T cells was minimally impaired compared to healthy controls. In vivo and in vitro varicella antigen-specific T cell responses were comparable to those of healthy controls, although a reduced level of T cell receptor excision circles suggested that recent thymic output was low. During long-term evaluation of the patient’s immunologic status, both the number of CD4+ and CD8+ T cells and T cell proliferation responses were stable and the patient remained healthy. This case demonstrates that multiple but restricted somatic reversions in T cell progenitors can improve the clinical phenotype of SCID-X1.

Keywords

Severe combined immunodeficiency reversion multiple 

Notes

Acknowledgements

We are grateful to the patient and his family for their participation. We also thank Takeda Pharmaceutical Company (Osaka, Japan) for kindly providing recombinant IL-2.

Authors’ contributions

T.K. performed experiments and wrote the paper. M.S. and Ka.I. performed experiments. R.N. designed the research, wrote the paper and analyzed data. Y.T. wrote the paper and analyzed data. T.M. treated the patient and analyzed data. S.O., Y.M., N.N., Ko.I, S.N., T.W. and A.Y. performed experiments and discussed the research. T.H. and T.N. designed the research.

Conflict of Interests

The authors declare no competing financial interests.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Tomoki Kawai
    • 1
  • Megumu Saito
    • 2
  • Ryuta Nishikomori
    • 1
    Email author
  • Takahiro Yasumi
    • 1
  • Kazushi Izawa
    • 1
  • Tomohiko Murakami
    • 3
  • Shigefumi Okamoto
    • 4
  • Yasuko Mori
    • 5
  • Noriko Nakagawa
    • 6
  • Kohsuke Imai
    • 7
  • Shigeaki Nonoyama
    • 8
  • Taizo Wada
    • 9
  • Akihiro Yachie
    • 9
  • Katsuyuki Ohmori
    • 10
  • Tatsutoshi Nakahata
    • 2
  • Toshio Heike
    • 1
  1. 1.Department of PediatricsKyoto University Graduate School of MedicineKyotoJapan
  2. 2.Clinical Application Department, Center for iPS Cell Research and Application, Institute for Integrated Cell-material SciencesKyoto UniversityKyotoJapan
  3. 3.Kawakita General HospitalTokyoJapan
  4. 4.Laboratory of Virology and Vaccinology, Division of Biomedical ResearchNational Institute of Biomedical InnovationOsakaJapan
  5. 5.Division of Clinical VirologyKobe University Graduate School of MedicineKobeJapan
  6. 6.Department of PediatricsJapan Self Defense Force Hospital FukuokaKasugaJapan
  7. 7.Department of Developmental Biology and PediatricsTokyo Medical and Dental University Graduate School of Medical and Dental SciencesSaitamaJapan
  8. 8.Department of PediatricsNational Defense Medical CollegeSaitamaJapan
  9. 9.Department of Pediatrics, Graduate School of Medical ScienceKanazawa UniversityKanazawaJapan
  10. 10.Department of Laboratory Medicine, Graduate School of MedicineKyoto UniversityKyotoJapan

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