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

Morinishi, Yoichi; Imai, Kohsuke; Nakagawa, Noriko; Sato, Hiroki; Horiuchi, Katsuyuki; Ohtsuka, Yoshitoshi; Kaneda, Yumi; Taga, Takashi; Hisakawa, Hiroaki; Miyaji, Ryosuke; Endo, Mikiya; Oh–ishi, Tsutomu; Kamachi, Yoshiro; Akahane, Koshi; Kobayashi, Chie; Tsuchida, Masahiro; Morio, Tomohiro; Sasahara, Yoji; Kumaki, Satoru; Ishigaki, Keiko; Yoshida, Makoto; Urabe, Tomonari; Kobayashi, Norimoto; Okimoto, Yuri; Reichenbach, Janine; Hashii, Yoshiko; Tsuji, Yoichiro; Kogawa, Kazuhiro; Yamaguchi, Seiji; Kanegane, Hirokazu; Miyawaki, Toshio; Yamada, Masafumi; Ariga, Tadashi; Nonoyama, Shigeaki

doi:10.1016/j.jpeds.2009.05.026

« Previous Next »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
- Department of Pediatrics, National Defense Medical College, Saitama, Japan
Kohsuke Imai, MD, PhD
- Department of Pediatrics, National Defense Medical College, Saitama, Japan
- Department of Medical Informatics, National Defense Medical College Hospital, Saitama, Japan
- Reprint requests: Dr Kohsuke Imai, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, Japan, 359-8513.
Noriko Nakagawa, MD
- Department of Pediatrics, National Defense Medical College, Saitama, Japan
Hiroki Sato, MHSc
- Department of Medical Informatics, National Defense Medical College Hospital, Saitama, Japan
Katsuyuki Horiuchi, MD, PhD
- Department of Pediatrics, National Defense Medical College, Saitama, Japan
Yoshitoshi Ohtsuka, MD, PhD
- Department of Pediatrics, Hyogo College of Medicine, Hyogo, Japan
Yumi Kaneda, MD
- Department of Pediatrics, Hyogo College of Medicine, Hyogo, Japan
Takashi Taga, MD, PhD
- Department of Pediatrics, Shiga University of Medical Science, Shiga, Japan
Hiroaki Hisakawa, MD, PhD
- Department of Pediatrics, Kochi University, Kochi, Japan
Ryosuke Miyaji, MD
- Department of Pediatrics, University of Occupational and Environmental Health, Fukuoka, Japan
Mikiya Endo, MD
- Department of Pediatrics, Iwate Medical University, Iwate, Japan
Tsutomu Oh–ishi, MD, PhD
- Division of Infectious Diseases, Immunology, and Allergy, Saitama Children's Medical Center, Saitama, Japan
Yoshiro Kamachi, MD, PhD
- Department of Pediatrics, Nagoya University Graduate School of Medicine, Aichi, Japan
Koshi Akahane, MD
- Department of Pediatrics, Yamanashi Prefectural Central Hospital, Yamanashi, Japan
Chie Kobayashi, MD, PhD
- Department of Pediatrics, Ibaraki Children's Hospital, Ibaraki, Japan
Masahiro Tsuchida, MD, PhD
- Department of Pediatrics, Ibaraki Children's Hospital, Ibaraki, Japan
Tomohiro Morio, MD, PhD
- Department of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan
Yoji Sasahara, MD, PhD
- Department of Pediatrics, Tohoku University, Miyagi, Japan
Satoru Kumaki, MD, PhD
- Department of Pediatrics, Tohoku University, Miyagi, Japan
Keiko Ishigaki, MD, PhD
- Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan
Makoto Yoshida, MD, PhD
- Department of Pediatrics, Asahikawa Medical College, Hokkaido, Japan
Tomonari Urabe, MD
- Department of Pediatrics, Kumamoto University, Kumamoto, Japan
Norimoto Kobayashi, MD, PhD
- Department of Interdisciplinary Medicine, Nagano Children's Hospital, Nagano, Japan
Yuri Okimoto, MD, PhD
- Department of Hematology/Oncology, Chiba Children's Hospital, Chiba, Japan
Janine Reichenbach, MD, PhD
- Department of Immunology/Hematology/BMT, University Children's Hospital Zurich, Zurich, Switzerland
Yoshiko Hashii, MD, PhD
- Department of Pediatrics, Osaka University, Osaka, Japan
Yoichiro Tsuji, MD, PhD
- Department of Pediatrics, National Defense Medical College, Saitama, Japan
Kazuhiro Kogawa, MD, PhD
- Department of Pediatrics, National Defense Medical College, Saitama, Japan
Seiji Yamaguchi, MD, PhD
- Department of Pediatrics, Shimane University, Shimane, Japan
Hirokazu Kanegane, MD, PhD
- Department of Pediatrics, University of Toyama, Toyama, Japan
Toshio Miyawaki, MD, PhD
- Department of Pediatrics, University of Toyama, Toyama, Japan
Masafumi Yamada, MD, PhD
- Department of Pediatrics, Hokkaido University, Hokkaido, Japan
Tadashi Ariga, MD, PhD
- Department of Pediatrics, Hokkaido University, Hokkaido, Japan
Shigeaki Nonoyama, MD, PhD
- Department of Pediatrics, National Defense Medical College, Saitama, Japan

Received 10 October 2008; received in revised form 22 April 2009; accepted 19 May 2009. published online 23 July 2009.

Objective

To assess the feasibility of T-cell receptor excision circles (TRECs) quantification for neonatal mass screening of severe combined immunodeficiency (SCID).

Study design

Real-time PCR based quantification of TRECs for 471 healthy control patients and 18 patients with SCID with various genetic abnormalities (IL2RG, JAK3, ADA, LIG4, RAG1) were performed, including patients with maternal T-cell engraftment (n = 4) and leaky T cells (n = 3).

Results

TRECs were detectable in all normal neonatal Guthrie cards (n = 326) at the levels of 10⁴ to 10⁵ copies/μg DNA. In contrast, TRECs were extremely low in all neonatal Guthrie cards (n = 15) and peripheral blood (n = 14) from patients with SCID, including those with maternal T-cell engraftment or leaky T cells with hypomorphic RAG1 mutations or LIG4 deficiency. There were no false-positive or negative results in this study.

Conclusion

TRECs quantification can be used as a neonatal mass screening for patients with SCID.

BCG, Bacillus Calmette-Guérin, BMT, Bone marrow transplantation, CMV, Cytomegalovirus, FISH, Fluorescent in situ hybridization, HSCT, Hematopoietic stem cell transplantation, PB, Peripheral blood, PCR, Polymerase chain reaction, sjTRECs, Signal joint TRECs, SCID, Severe combined immunodeficiency, TCR, T-cell receptor, TRECs, T-cell receptor excision circles, UCB, Umbilical cord blood

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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

Refers to article:

Long-term Clinical Outcome of Patients with Severe Combined Immunodeficiency Who Received Related Donor Bone Marrow Transplants without Pretransplant Chemotherapy or Post-transplant GVHD Prophylaxis , 12 October 2009
Mary Dell Railey, Yuliya Lokhnygina, Rebecca H. Buckley
The Journal of Pediatrics December 2009 (Vol. 155, Issue 6, Pages 834-840.e1)