T-cell receptor excision circles in primary immunodeficiencies and other T-cell immune disorders

Somech, Raz

doi:10.1097/aci.0b013e32834c233a

Cited by 46 publications

(33 citation statements)

References 54 publications

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“…Our results indicate that these markers can be used to accurately estimate different intra-thymic capacities for assessing T cell function. TREC, a thymus by-product which quantifies recent thymic emigrants, is extensively used to assess primary T cell immunodeficiency and other processes in which T cell immunity is disrupted, including HIV, aging, bone marrow transplantation and others [18]. Arellano et al [17] have shown that, indeed, peripheral TREC levels well reflect thymic function and stable analytes, as demonstrated by their correlation with intra-thymic TREC values.…”

Section: Discussionmentioning

confidence: 97%

Insight into normal thymic activity by assessment of peripheral blood samples

et al. 2014

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The thymus is a highly specialized organ for T cell receptor (TCR) rearrangement and selection mechanisms that ensure the formation of functional and self-tolerant cells. Little is known about how peripheral blood assessment of thymic function reflects thymus activity during infancy. We compared thymic function-related markers in the thymus with those in peripheral blood in order to check their correlations. We concomitantly blood samples from immunocompetent infants who underwent cardiac surgery that involved thymectomy. The studied thymic markers included TCR excision circles (TRECs), four different TCRD (TCR delta chain) gene rearrangements, the TCR repertoire, regulatory T cells (Tregs, defined as the CD4+CD25+FOXP3+ cell population) and real-time quantitative polymerase chain reaction (RQ-PCR) mRNA expression of forkhead box P3 (FOXP3). Twenty patients were enrolled in this study. Their mean age at the time of the surgery was 3 months/5 days ± 3 months/18 days. There was a significant correlation between thymic and peripheral blood levels of TREC, all four TCRD gene rearrangements and the amount of Tregs. The levels of these parameters were significantly higher in the thymus than those detected in the peripheral blood. The TCR repertoire distribution in both samples was similar. FOXP3 mRNA levels in the thymus and peripheral blood correlated well. Our findings demonstrated a strong and significant correlation between peripheral blood and intra-thymic activity parameters during infancy. Assessment of these parameters in peripheral blood can be used to accurately estimate different intra-thymic capacities for assessing T cell function in health and disease.

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Section: Discussionmentioning

confidence: 97%

Insight into normal thymic activity by assessment of peripheral blood samples

et al. 2014

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“…Assays for the copy number of TRECs in peripheral blood are now conducted in clinical and research laboratories to monitor naïve T cells emigrating from the thymus (reviewed by [18, 22]). Detecting absence of TRECs in newborns by population-based screening of their routinely collected DBS permits early diagnosis of SCID from otherwise unsuspected and asymptomatic newborns, making possible prompt intervention to prevent severe infections and provide definitive treatment with optimal outcome [32].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, other newborn conditions with low numbers of T cells are also revealed by TREC screening. Furthermore, later in life, serial measurement of TRECs by qPCR can be used to document the status of thymic production of T cells in a variety of patients, such as those who have undergone hematopoietic cell transplantation (HCT) or other interventions such as treatments for malignancy or HIV infection ([1, 5, 16] and reviewed by [17, 18]).…”

Section: Introductionmentioning

confidence: 99%

Cellular calibrators to quantitate T-cell receptor excision circles (TRECs) in clinical samples

Punwani

González-Espinosa

Comeau

et al. 2012

Molecular Genetics and Metabolism

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T cell receptor excision circles (TRECs) are circular DNA molecules formed during rearrangement of the T cell receptor (TCR) genes during lymphocyte development. Copy number of the junctional portion of the δRec-ψJα TREC, assessed by quantitative PCR (qPCR) using DNA from dried blood spots (DBS), is a biomarker for newly formed T cells and absent or low numbers of TRECs indicate SCID (severe combined immunodeficiency) or T lymphocytopenia. No quantitation standard for TRECs exists. To permit comparison of TREC qPCR results with a reliable method for counting TRECs across different laboratories, we sought to construct a stable cell line containing a normal human chromosomal constitution and a single copy of the TREC junction sequence. A human EBV (Epstein Barr virus) transformed B cell line was transduced with a lentivirus encoding mCherry fluorescence, puromycin resistance and the δRec-ψJα TREC sequence. A TREC-EBV cell line, with each cell carrying a single lentiviral insertion was established, expanded and shown to have one TREC copy per diploid genome. Graded numbers of TREC-EBV cells added to aliquots of T lymphocyte depleted blood showed TREC copy number proportional to TREC-EBV cell number. TREC-EBV cells, therefore, constitute a reproducible cellular calibrator for TREC assays, useful for both population-based screening for severe combined immunodeficiency and evaluation of naïve T cell production in clinical settings.

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“…The disease is fatal unless prompt measures are taken at very early age. Hence, early diagnosis and intervention would improve the outcome [83]. In this regard, TREC was used for the first time as a screening tool by McGhee et al [84].…”

Section: T Cell Reconstitution After Hsct and T Cell Receptor Excimentioning

confidence: 99%

“…Currently, TREC has proven to be the best non-invasive, feasible screening tool for SCID and has been implemented clinically in the USA. TREC analysis will most likely become a worldwide screening tool for SCID [83]. …”

Section: T Cell Reconstitution After Hsct and T Cell Receptor Excimentioning

confidence: 99%

T Cell Receptor Excision Circle (TREC) Monitoring after Allogeneic Stem Cell Transplantation; a Predictive Marker for Complications and Clinical Outcome

Gaballa

Sundin

Stikvoort

et al. 2016

IJMS

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Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established treatment modality for a variety of malignant diseases as well as for inborn errors of the metabolism or immune system. Regardless of disease origin, good clinical effects are dependent on proper immune reconstitution. T cells are responsible for both the beneficial graft-versus-leukemia (GVL) effect against malignant cells and protection against infections. The immune recovery of T cells relies initially on peripheral expansion of mature cells from the graft and later on the differentiation and maturation from donor-derived hematopoietic stem cells. The formation of new T cells occurs in the thymus and as a byproduct, T cell receptor excision circles (TRECs) are released upon rearrangement of the T cell receptor. Detection of TRECs by PCR is a reliable method for estimating the amount of newly formed T cells in the circulation and, indirectly, for estimating thymic function. Here, we discuss the role of TREC analysis in the prediction of clinical outcome after allogeneic HSCT. Due to the pivotal role of T cell reconstitution we propose that TREC analysis should be included as a key indicator in the post-HSCT follow-up.

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T-cell receptor excision circles in primary immunodeficiencies and other T-cell immune disorders

Cited by 46 publications

References 54 publications

Insight into normal thymic activity by assessment of peripheral blood samples

Insight into normal thymic activity by assessment of peripheral blood samples

Cellular calibrators to quantitate T-cell receptor excision circles (TRECs) in clinical samples

T Cell Receptor Excision Circle (TREC) Monitoring after Allogeneic Stem Cell Transplantation; a Predictive Marker for Complications and Clinical Outcome

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