Abstract
Infants born with T cell lymphopenias, especially severe combined immunodeficiency (SCID) are at risk for serious, often fatal infections without intervention within the first year or two of life. The majority of these disorders can be detected through the use of the T cell recombination excision circle assay (TREC assay.) The TREC assay detects the presence of non-replicating, episomal DNA that is formed during T cell development. This assay initially developed to measure thymic output during aging and HIV infection, has undergone modifications for the purpose of newborn screening (NBS) for SCID. To meet the requirements for inclusion on NBS panels, the assay needed to utilize blood from dried blood spots on NBS cards, and be both sensitive and specific, avoiding the costs of false positives. Currently, the assay relies upon real time, quantitative PCR (RT-qPCR) to detect TRECs in punches taken from dried blood spots. This review seeks to highlight some of the early work leading up to the initial implementation of the TREC assay for SCID detection, and the subsequent revisions made to optimize the assay.
Highlights
Newborn screening (NBS) public health programs are currently used to detect over 50 different conditions that may be present but not immediately evident at birth
The T cell receptor excision circle assay (TREC) assay for NBS of Severe Combined Immunodeficiency (SCID)/severe T cell lymphopenia uses real-time quantitative PCR (RT-qPCR) of DNA extracted from the dried blood spot (DBS) to quantitate a non-replicating episomal excision circle formed during the generation of the αβ T cell receptor in the thymus
Samples testing positive for SCID via the TREC assay would be confirmed by a second test measuring DBS serum or plasma interleukin-7 (IL-7) levels which can be elevated in SCID
Summary
Newborn screening (NBS) public health programs are currently used to detect over 50 different conditions that may be present but not immediately evident at birth. For population-based screening, the T cell receptor excision circle assay (TREC) assay is used to detect SCID or severe forms of T cell lymphopenia. The TREC assay for NBS of SCID/severe T cell lymphopenia (sTCL) uses real-time quantitative PCR (RT-qPCR) of DNA extracted from the DBS to quantitate a non-replicating episomal excision circle formed during the generation of the αβ T cell receptor in the thymus. TCRα gene rearrangement occurs last, deleting the TCRδ locus and results in expression of a functional α:β TCR on the cell surface. Following negative selection, these naïve T-cells undergo very little expansion before moving from the thymus to the periphery. The measurement of TRECs distinguishes between homeostatic expansion of T cells in the periphery compared to the production of newly formed, naïve T cells
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