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Trends in TREC values according to age and gender in Chinese children and their clinical applications

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Abstract

T cell receptor excision circles (TRECs) are small circularized DNA elements produced during rearrangement of T cell receptor (TCR) genes. Because TRECs are fairly stable, do not replicate during mitosis, and are not diluted during division of naïve T cells (Dion et al. [1]), they are suitable for assessing the number of newly formed T cells (Ping and Denise [2]). In this study, we detected TRECs in 521 healthy Chinese children aged 0–18 years in different clinical settings. The TRECs decrease with aging and show lower levels in preterm and low birth weight (BW) babies compared to those in full-term infants, while the preterm babies can also show comparable levels of TRECs when they have a gestation age (GA)–matched BW. We found a strong correlation between TRECs and peripheral CD4 naïve T cell numbers, which was age-related. We also analyzed the TRECs in different PIDs. Since T cell defects vary in PIDs, TREC levels change inconsistently. For example, in Wiskott-Aldrich syndrome (WAS), combining the level of TREC with lymphocyte subsets can help to distinguish subtypes of disease.

Conclusion: We established the reference value range for TRECs by evaluating children below 18 years old in China, which could be used to screen for PIDs during early life.

What is Known:

• The TREC levels are decreased with age, and there is a positive correlation between TRECs and the numbers of naïve T cells.

What is New:

• This is the largest study to determine TREC reference levels in healthy Chinese pediatric, we provide solid data showing a correlation between CD4 naïve T cell counts and TREC levels according to age. We point out the GA matched BW is need to be considered during the SCID newborn screening. We are the first group showed that TREC levels can help clinician distinguish different WAS phenotype.

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Abbreviations

APDS:

Activated PI3Kδ syndrome

BW:

Birth weight

CIDs:

Combined immunodeficiency

CGD:

Chronic granulomatous disease

GA:

Gestation age

GOF:

Gain-of-function

HSCT:

Hematopoietic stem cell transplantation

PIDs:

Primary immunodeficiency diseases

qPCR:

Quantitative PCR

SCID:

Severe combined immunodeficiencies

STAT1:

Signal transducer and activator of transcription 1

TRECs:

T cell receptor excision circles

TCR:

T cell receptor

XLA:

X-linked agammaglobulinemia

XLN:

X-linked neutropenia

XLT:

X-linked thrombocytopenia

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Acknowledgements

We are grateful to all the healthy participants, the patients, and their families for their continuous corporation in this study. We thank the members of the laboratory for their technical assistance. We thank doctors and nurses for their generous supporting this project.

Funding

This work was supported by the Science and Technology Research Program of Chongqing Municipal Education Commission (KJZD-M201800401) and Chongqing. Postgraduate Research and Innovation Project (CYB18157).

Author information

Authors and Affiliations

  1. Department of Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China

    Qin Zhao, Rongxin Dai, Yanan Li, Yanping Wang, Xuemei Chen, Zhou Shu, Lina Zhou, Yuan Ding & Xiaodong Zhao

  2. Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, China

    Qin Zhao, Rongxin Dai, Yanan Li, Yanping Wang, Xuemei Chen, Zhou Shu, Lina Zhou, Yuan Ding & Xiaodong Zhao

  3. Department of Rheumatology and Immunology, Children’s Hospital of Chongqing Medical University, No. 136, Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, China

    Rongxin Dai, Zhou Shu, Xuemei Tang & Xiaodong Zhao

  4. Department of Health Management, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, China

    Yuan Ding

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  1. Qin Zhao
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Correspondence to Xiaodong Zhao.

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Informed consent was obtained from all individual participants included in the study. This study was conducted in accordance with the tenets of the Declaration of Helsinki and was approved by the ethics committee of Chongqing Medical University.

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Zhao, Q., Dai, R., Li, Y. et al. Trends in TREC values according to age and gender in Chinese children and their clinical applications. Eur J Pediatr 181, 529–538 (2022). https://doi.org/10.1007/s00431-021-04223-8

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