Neonatal Levels of T-cell Receptor Excision Circles (TREC) in Patients with 22q11.2 Deletion Syndrome and Later Disease Features
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.
KeywordsT-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
fluorescent in situ hybridization
Severe combined immunodeficiency
DNA Purification solution
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.
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