Journal of Clinical Immunology

, Volume 35, Issue 4, pp 408–415 | Cite as

Neonatal Levels of T-cell Receptor Excision Circles (TREC) in Patients with 22q11.2 Deletion Syndrome and Later Disease Features

  • Kiran A. Gul
  • Torstein Øverland
  • Liv Osnes
  • Lars O. Baumbusch
  • Rolf D. Pettersen
  • Kari Lima
  • Tore G. Abrahamsen
Original Research



Newborns with severe T-cell lymphopenia, including those with 22q11.2 deletion syndrome (DS), have low numbers of T-cell receptor excision circles (TRECs). The aim of this study was to determine a possible correlation between neonatal TRECs in 22q11.2DS and the development of different phenotypes to elucidate the prognostic value of TREC in this disease.


In this national survey including 46 patients with 22q11.2DS born after 2005, TREC levels were determined using stored newborn screening blood spots on filter cards. Patients were grouped into quartiles according to their TREC values, except the two infants with thymus aplasia.


The two patients with thymic aplasia had no detectable TREC. The rest had no severe clinical immunodeficiency. There was a significant correlation between low TRECs and the proportion of patients with CD3+CD4+T-cells below the 5th percentile of healthy infants (p = 0.027) as well as the proportion with an abnormal thymus feature either no thymus or remnant thymus as observed during heart surgery (p = 0.022). Significantly lower TRECs (p = 0.019) were found in patients with cardiac defects compared to no such defects. Patients within the lowest quartile of TREC values (<71 TRECs/μL, n = 11) had more frequent severe cardiac defects than the other quartiles (p = 0.010). Eight of these patients in the lowest quartile needed an operation/intervention within two weeks after birth or died because of a cardiac defect.


The low TREC values not only correlate with decreased T-cell immunity, but also with the occurrence of heart defects in the patients.


T-cell receptor excision circles 22q11.2 deletion syndrome cardiac defect thymus newborn screening 



Centre of disease control

CGH array

Comparative genomic hybridization array






Dried blood spot


Deletion syndrome


fluorescent in situ hybridization


Severe combined immunodeficiency


DNA Purification solution


Elution solution


T-Box 1


T-cell receptor


T-cell receptor excision circles


major aortopulmonary collateral arteries


Ventricle septum defect



We appreciate the support of Jacalyn Gerstel-Thompson, University of Massachusetts Medical School. We are grateful to Leiv Sandvik, Gaute Nesse for his help with the plasmid preparation, and Grethe Dyrhaug and Monica Åsegg-Atneosen for technical guidance. We also thank Marianne Wright for her help throughout the research and the genetic institutions in Norway, in particular Teresia Wangensteen, for the help with inclusion and genetic characterization of the patients.

Conflicts of Interest

All the authors confirm that no conflict of interest exists.

Supplementary material

10875_2015_153_Fig2_ESM.gif (59 kb)

There is a significant correlation between TREC quartiles and CD3 + CD4+ T-cells (p = 0.027). (GIF 58 kb)

10875_2015_153_MOESM1_ESM.docx (20 kb)
High resolution image (DOCX 20 kb)
10875_2015_153_MOESM2_ESM.tif (80 kb)
ESM 1 (TIFF 80 kb)


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Kiran A. Gul
    • 1
    • 2
  • Torstein Øverland
    • 3
  • Liv Osnes
    • 4
  • Lars O. Baumbusch
    • 1
  • Rolf D. Pettersen
    • 2
  • Kari Lima
    • 3
    • 5
  • Tore G. Abrahamsen
    • 3
    • 6
  1. 1.Department of Pediatric Research, Women and Children’s DivisionOslo University Hospital RikshospitaletOsloNorway
  2. 2.Norwegian National Unit for Newborn Screening, Women and Children’s DivisionOslo University Hospital RikshospitaletOsloNorway
  3. 3.Department of Pediatric Medicine, Women and Children’s DivisionOslo University Hospital RikshospitaletOsloNorway
  4. 4.Department of ImmunologyOslo University Hospital RikshospitaletOsloNorway
  5. 5.Department of Endocrinology, Division of MedicineAkershus University HospitalLørenskogNorway
  6. 6.Faculty of MedicineUniversity of OsloOsloNorway

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