Introduction
The thymus provides a suitable microenvironment for maturation of T cells; therefore, thymic output may reflect thymus function. T cell receptor excision circles (TRECs) are circular DNA segments generated in T cells during sequential rearrangement of the variable V, D, and J segments of TCR genes. About 70% of all newly produced T cells are TREC-positive. These circularized DNA elements cannot replicate or be stored in the cells3. Thus, quantitation of TRECs is an excellent surrogate marker of the number of naïve T cells that have emigrated recently from the thymus4.
Since measurement of TRECs can be done quickly by real-time quantitative PCR (RT-qPCR), TRECs levels have been used to assess thymic output under healthy and disease conditions; they are especially useful for diagnosis and management of T cell-related disorders5. In recent years, TRECs have been used to screen newborns for SCID6. Low TRECs levels have been detected in preterm newborns and low birth weight (BW) babies. Newborns with Down’s syndrome and ataxia telangiectasia have low TRECs levels7,8.
As TRECs are a marker of T cell reconstitution, levels should predict occurrence of GVHD after HSCT. Indeed, patients with low TRECs levels after HSCT are more likely to suffer GVHD9,10. Assessing trends in TRECs levels according to age is used as a forensic investigation tool to estimate age11. TRECs levels could be used to distinguish between benign and malignant diseases; indeed, studies show that levels in patients with acute lymphocytic leukemia and acute myeloid leukemia are lower than those in healthy persons12. In addition, TRECs analysis has been applied to autoimmune diseases. TRECs levels in patients with systemic lupus erythematosus fall as disease activity increases13. Levels are also low in patients with autoimmune thyroiditis. However, levels in those with autoimmune type 1 diabetes are higher than those in healthy controls14.
Several studies have examined thymic function in healthy children and adults15,16. However, in China, we have no reference values for TRECs in different pediatric age groups. Therefore, it is difficult to determine a cut-off value for TRECs in a clinical setting. Also, it is not completely clear which diseases impact TRECs values. Here, we examined trends in TRECs levels in 475 healthy children (aged 0–18 years) according to age; the cohort included premature newborns and low BW newborns. Combined with analysis of lymphocyte subsets, we demonstrated a strong correlation between TRECs levels and CD4 naïve T cell numbers. To test the significance of these findings in a clinical setting, we evaluated TRECs levels in patients with different PIDs and patients with PIDs treated with HSCT.