The Journal of Pediatrics
Volume 155, Issue 6 , Pages 829-833 , December 2009

Identification of Severe Combined Immunodeficiency by T-Cell Receptor Excision Circles Quantification Using Neonatal Guthrie Cards

  • Yoichi Morinishi, MD, PhD

      Affiliations

    • Department of Pediatrics, National Defense Medical College, Saitama, Japan
    • ,
  • Kohsuke Imai, MD, PhD

      Affiliations

    • Department of Pediatrics, National Defense Medical College, Saitama, Japan
    • Department of Medical Informatics, National Defense Medical College Hospital, Saitama, Japan
    • Corresponding Author InformationReprint requests: Dr Kohsuke Imai, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, Japan, 359-8513.
    • ,
  • Noriko Nakagawa, MD

      Affiliations

    • Department of Pediatrics, National Defense Medical College, Saitama, Japan
    • ,
  • Hiroki Sato, MHSc

      Affiliations

    • Department of Medical Informatics, National Defense Medical College Hospital, Saitama, Japan
    • ,
  • Katsuyuki Horiuchi, MD, PhD

      Affiliations

    • Department of Pediatrics, National Defense Medical College, Saitama, Japan
    • ,
  • Yoshitoshi Ohtsuka, MD, PhD

      Affiliations

    • Department of Pediatrics, Hyogo College of Medicine, Hyogo, Japan
    • ,
  • Yumi Kaneda, MD

      Affiliations

    • Department of Pediatrics, Hyogo College of Medicine, Hyogo, Japan
    • ,
  • Takashi Taga, MD, PhD

      Affiliations

    • Department of Pediatrics, Shiga University of Medical Science, Shiga, Japan
    • ,
  • Hiroaki Hisakawa, MD, PhD

      Affiliations

    • Department of Pediatrics, Kochi University, Kochi, Japan
    • ,
  • Ryosuke Miyaji, MD

      Affiliations

    • Department of Pediatrics, University of Occupational and Environmental Health, Fukuoka, Japan
    • ,
  • Mikiya Endo, MD

      Affiliations

    • Department of Pediatrics, Iwate Medical University, Iwate, Japan
    • ,
  • Tsutomu Oh–ishi, MD, PhD

      Affiliations

    • Division of Infectious Diseases, Immunology, and Allergy, Saitama Children's Medical Center, Saitama, Japan
    • ,
  • Yoshiro Kamachi, MD, PhD

      Affiliations

    • Department of Pediatrics, Nagoya University Graduate School of Medicine, Aichi, Japan
    • ,
  • Koshi Akahane, MD

      Affiliations

    • Department of Pediatrics, Yamanashi Prefectural Central Hospital, Yamanashi, Japan
    • ,
  • Chie Kobayashi, MD, PhD

      Affiliations

    • Department of Pediatrics, Ibaraki Children's Hospital, Ibaraki, Japan
    • ,
  • Masahiro Tsuchida, MD, PhD

      Affiliations

    • Department of Pediatrics, Ibaraki Children's Hospital, Ibaraki, Japan
    • ,
  • Tomohiro Morio, MD, PhD

      Affiliations

    • Department of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan
    • ,
  • Yoji Sasahara, MD, PhD

      Affiliations

    • Department of Pediatrics, Tohoku University, Miyagi, Japan
    • ,
  • Satoru Kumaki, MD, PhD

      Affiliations

    • Department of Pediatrics, Tohoku University, Miyagi, Japan
    • ,
  • Keiko Ishigaki, MD, PhD

      Affiliations

    • Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan
    • ,
  • Makoto Yoshida, MD, PhD

      Affiliations

    • Department of Pediatrics, Asahikawa Medical College, Hokkaido, Japan
    • ,
  • Tomonari Urabe, MD

      Affiliations

    • Department of Pediatrics, Kumamoto University, Kumamoto, Japan
    • ,
  • Norimoto Kobayashi, MD, PhD

      Affiliations

    • Department of Interdisciplinary Medicine, Nagano Children's Hospital, Nagano, Japan
    • ,
  • Yuri Okimoto, MD, PhD

      Affiliations

    • Department of Hematology/Oncology, Chiba Children's Hospital, Chiba, Japan
    • ,
  • Janine Reichenbach, MD, PhD

      Affiliations

    • Department of Immunology/Hematology/BMT, University Children's Hospital Zurich, Zurich, Switzerland
    • ,
  • Yoshiko Hashii, MD, PhD

      Affiliations

    • Department of Pediatrics, Osaka University, Osaka, Japan
    • ,
  • Yoichiro Tsuji, MD, PhD

      Affiliations

    • Department of Pediatrics, National Defense Medical College, Saitama, Japan
    • ,
  • Kazuhiro Kogawa, MD, PhD

      Affiliations

    • Department of Pediatrics, National Defense Medical College, Saitama, Japan
    • ,
  • Seiji Yamaguchi, MD, PhD

      Affiliations

    • Department of Pediatrics, Shimane University, Shimane, Japan
    • ,
  • Hirokazu Kanegane, MD, PhD

      Affiliations

    • Department of Pediatrics, University of Toyama, Toyama, Japan
    • ,
  • Toshio Miyawaki, MD, PhD

      Affiliations

    • Department of Pediatrics, University of Toyama, Toyama, Japan
    • ,
  • Masafumi Yamada, MD, PhD

      Affiliations

    • Department of Pediatrics, Hokkaido University, Hokkaido, Japan
    • ,
  • Tadashi Ariga, MD, PhD

      Affiliations

    • Department of Pediatrics, Hokkaido University, Hokkaido, Japan
    • ,
  • Shigeaki Nonoyama, MD, PhD

      Affiliations

    • Department of Pediatrics, National Defense Medical College, Saitama, Japan

Received 10 October 2008 ,Revised 22 April 2009 ,Accepted 19 May 2009.

References 

  1. Fischer A, Le Deist F, Hacein-Bey-Abina S, Andre-Schmutz I, BasileGde S, de Villartay JP, et al. Severe combined immunodeficiency: a model disease for molecular immunology and therapy. Immunol Rev. 2005;203:98–109
  2. Buckley RH. Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution. Annu Rev Immunol. 2004;22:625–655
  3. Buckley RH, Schiff SE, Schiff RI, Markert L, Williams LW, Roberts JL, et al. Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med. 1999;340:508–516
  4. Antoine C, Muller S, Cant A, Cavazzana-Calvo M, Veys P, Vossen J, et al. Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968-99. Lancet. 2003;361:553–560
  5. Myers LA, Patel DD, Puck JM, Buckley RH. Hematopoietic stem cell transplantation for severe combined immunodeficiency in the neonatal period leads to superior thymic output and improved survival. Blood. 2002;99:872–878
  6. Chan K, Puck JM. Development of population-based newborn screening for severe combined immunodeficiency. J Allergy Clin Immunol. 2005;115:391–398
  7. McGhee SA, Stiehm ER, Cowan M, Krogstad P, McCabe ER. Two-tiered universal newborn screening strategy for severe combined immunodeficiency. Mol Genet Metab. 2005;86:427–430
  8. Buckley RH, Schiff RI, Schiff SE, Markert ML, Williams LW, Harville TO, et al. Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. J Pediatr. 1997;130:378–387
  9. Patel DD, Gooding ME, Parrott RE, Curtis KM, Haynes BF, Buckley RH. Thymic function after hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med. 2000;342:1325–1332
  10. de Villartay JP, Hockett RD, Coran D, Korsmeyer SJ, Cohen DI. Deletion of the human T-cell receptor delta-gene by a site-specific recombination. Nature. 1988;335:170–174
  11. Douek DC, McFarland RD, Keiser PH, Gage EA, Massey JM, Haynes BF, et al. Changes in thymic function with age and during the treatment of HIV infection. Nature. 1998;396:690–695
  12. McFarland RD, Douek DC, Koup RA, Picker LJ. Identification of a human recent thymic emigrant phenotype. Proc Natl Acad Sci U S A. 2000;97:4215–4220
  13. Hazenberg MD, Verschuren MC, Hamann D, Miedema F, van Dongen JJ. T cell receptor excision circles as markers for recent thymic emigrants: basic aspects, technical approach, and guidelines for interpretation. J Mol Med. 2001;79:631–640
  14. Hazenberg MD, Otto SA, CohenStuart JW, Verschuren MC, Borleffs JC, Boucher CA, et al. Increased cell division but not thymic dysfunction rapidly affects the T-cell receptor excision circle content of the naive T cell population in HIV-1 infection. Nat Med. 2000;6:1036–1042
  15. de Villartay JP, Lim A, Al-Mousa H, Dupont S, Dechanet-Merville J, Coumau-Gatbois E, et al. A novel immunodeficiency associated with hypomorphic RAG1 mutations and CMV infection. J Clin Invest. 2005;115:3291–3299
  16. Ehl S, Schwarz K, Enders A, Duffner U, Pannicke U, Kuhr J, et al. A variant of SCID with specific immune responses and predominance of gamma delta T cells. J Clin Invest. 2005;115:3140–3148
  17. Giblett ER, Anderson JE, Cohen F, Pollara B, Meuwissen HJ. Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. Lancet. 1972;2:1067–1069
  18. Hershfield MS. Genotype is an important determinant of phenotype in adenosine deaminase deficiency. Curr Opin Immunol. 2003;15:571–577
  19. McGhee SA, Stiehm ER, McCabe ER. Potential costs and benefits of newborn screening for severe combined immunodeficiency. J Pediatr. 2005;147:603–608

 Supported by grants from the Ministry of Defense, Ministry of Health, Labour and Welfare Kawano Masanori Foundation for Promotion of Pediatrics, Jeffrey Modell Foundation, and The Mother and Child Health Foundation.

 The authors declare no conflicts of interest.

PII: S0022-3476(09)00505-8

doi: 10.1016/j.jpeds.2009.05.026

The Journal of Pediatrics
Volume 155, Issue 6 , Pages 829-833 , December 2009

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