The TREC/KREC Assay for the Diagnosis and Monitoring of Patients with DiGeorge Syndrome

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Authors	FROŇKOVÁ Eva KLOCPERK Adam SVATOŇ Michael NOVÁKOVÁ Michaela KOTROVÁ Michaela KAYSEROVÁ Jana KALLNA Tomáš KESLOVÁ Petra VOTAVA Filip VINOHRADSKÁ Hana FREIBERGER Tomáš MEJSTRIKOVÁ Eva TRKA Jan ŠEDIVÁ Anna
Year of publication	2014
Type	Article in Periodical
Magazine / Source	Plos one
MU Faculty or unit	Central European Institute of Technology
Citation
Web	http://www.plosone.org/article/fetchObject.action?uri=info:doi/10.1371/journal.pone.0114514&representation=PDF
Doi	http://dx.doi.org/10.1371/journal.pone.0114514
Field	Immunology
Keywords	T-CELL-RECEPTOR; MINIMAL RESIDUAL DISEASE; DELETION SYNDROME; EXCISION CIRCLES; THYMIC OUTPUT; IMMUNODEFICIENCY; TRANSPLANTATION; PROLIFERATION; REPERTOIRES; CHILDREN
Attached files	ZVV_2014_246_1231783_The_TREC_KREC.pdf
Description	DiGeorge syndrome (DGS) presents with a wide spectrum of thymic pathologies. Nationwide neonatal screening programs of lymphocyte production using T-cell recombination excision circles (TREC) have repeatedly identified patients with DGS. We tested what proportion of DGS patients could be identified at birth by combined TREC and kappa-deleting element recombination circle (KREC) screening. Furthermore, we followed TREC/KREC levels in peripheral blood (PB) to monitor postnatal changes in lymphocyte production. Methods: TREC/KREC copies were assessed by quantitative PCR (qPCR) and were related to the albumin control gene in dry blood spots (DBSs) from control (n=56), severe immunodeficiency syndrome (SCID, n=10) and DGS (n=13) newborns. PB was evaluated in DGS children (n=32), in diagnostic samples from SCID babies (n=5) and in 91 controls. Results: All but one DGS patient had TREC levels in the normal range at birth, albeit quantitative TREC values were significantly lower in the DGS cohort. One patient had slightly reduced KREC at birth. Postnatal DGS samples revealed reduced TREC numbers in 5 of 32 (16%) patients, whereas KREC copy numbers were similar to controls. Both TREC and KREC levels showed a more pronounced decrease with age in DGS patients than in controls (p<0.0001 for both in a linear model). DGS patients had higher percentages of NK cells at the expense of T cells (p<0.0001). The patients with reduced TREC levels had repeated infections in infancy and developed allergy and/or autoimmunity, but they were not strikingly different from other patients. In 12 DGS patients with paired DBS and blood samples, the TREC/KREC levels were mostly stable or increased and showed similar kinetics in respective patients. Conclusions: The combined TREC/KREC approach with correction via control gene identified 1 of 13 (8%) of DiGeorge syndrome patients at birth in our cohort. The majority of patients had TREC/KREC levels in the normal range.