T cell receptor excision circles as a tool for evaluating thymic function in young children

Abstract

The thymus is a primary lymphoid organ responsible for the maturation of T cells as well as the immunological central tolerance. It is in the antenatal period and infancy that it plays its major role. In clinical practice, T cell receptor excision circles (TRECs) are considered a direct and reliable measure of the thymic function. TRECs are a by-product of DNA formation in gene rearrangement of T cell receptors. They are stable and they do not duplicate during mitosis, representing the recent emigrant T cells from the thymus. Despite their importance, TRECs have been neglected by physicians and there is a lack of data regarding thymic function during infancy of healthy children. In order to evaluate thymic function in the first years of life, we propose measuring TRECs as a valuable tool. One hundred and three blood samples from children and adolescents between 3 months and 20 years of age were analyzed. The mean TRECs count was 136.77±96.7 copies of TRECs/μL of DNA. The individuals between 0 and 5 years of age had significantly higher TRECs values than those between 10 and 20 years of age. No significant difference was observed in TRECs values among age groups below 5 years of age. An inverse correlation between TRECs and age was found (r=0.3 P=0.003). These data highlight and validate the evidence of decreased thymus function with age, even during infancy. Awareness should be raised with this important albeit ignored organ.

Low T‐cell receptor excision circles (TREC) in children and adolescents with immune thrombocytopenia

“…Our data is in line with those previously shown for males 7 . In addition, when ITP patients were stratified by age group, there were significant differences between patients and controls (Fig 1D), but not among ITP patients ( P = 0·07) as is expected with the decrease in TREC due to ageing 3,7 . Even the group of ITP patients under four years of age, in which thymopoiesis is expected to be prominent, had a lower number of TREC copies (median 36 copies/μl, range 13–61).…”

“…The same was observed when compared with controls (Fig 1C). Our data is in line with those previously shown for males 7 . In addition, when ITP patients were stratified by age group, there were significant differences between patients and controls (Fig 1D), but not among ITP patients ( P = 0·07) as is expected with the decrease in TREC due to ageing 3,7 .…”

“…They have been used as a biomarker of thymus function in several pathological processes such as: in newborn screening tests for primary immunodeficiencies (PID); to evaluate T cell reconstitution during antiretroviral therapy of AIDS; after bone marrow transplantation; and to clarify autoimmune disease pathogenesis 3‐6 . Although thymus undergoes anatomical and functional involutions after the third decade of life, it is still possible to detect some function, even in senescence 3,7 . Therefore, the numbers of TREC copies were quantified in children and adolescents with ITP and relationships were established with age at enrolment, age at disease onset, disease classification, and outcome.…”

A Critical Review on the Standardization and Quality Assessment of Nonfunctional Laboratory Tests Frequently Used to Identify Inborn Errors of Immunity

“…Quantification of the copy number of T cell receptor excision circles (TREC) in peripheral blood, which is usually performed by quantitative real-time polymerase chain reaction (qRT-PCR), has been shown to be an effective tool for the early identification of severe T lymphocyte deficiencies. Quantitative analysis of TREC is frequently used to: i) estimate the thymopoiesis rate in newborn screening tests for SCID ( 145 – 147 ); ii) assess thymus involvement in autoimmune diseases ( 148 , 149 ); and iii) evaluate T cell reconstitution during acquired immunodeficiency syndrome antiretroviral therapy and after bone marrow transplantation ( 150 – 154 ).…”

Trends in TRECs values according to age and gender in Chinese children, and their clinical application

“…Several studies have examined thymic function in healthy children and adults 15,16 . However, in China, we have no reference values for TRECs in different pediatric age groups.…”