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.