# T-Cell Receptor Excision Circle/Kappa-Deleting Recombination Excision Circle-Based Newborn Screening Program for Severe Combined Immunodeficiency in Kumamoto, Japan

## TL;DR

This study evaluates a new screening program in Japan using TREC and KREC measurements to detect severe immunodeficiencies in newborns.

## Contribution

The study introduces a combined TREC/KREC-based newborn screening program for detecting T- and B-cell immunodeficiencies.

## Key findings

- Three newborns (0.007%) were diagnosed with T-cell lymphopenia using TREC-based screening.
- One newborn (0.008%) was diagnosed with X-linked agammaglobulinemia using combined TREC/KREC screening.
- Maternal azathioprine exposure and low birth weight were found to affect TREC/KREC levels.

## Abstract

Severe combined immunodeficiency (SCID) is a life-threatening hereditary disorder that requires early diagnosis and intervention. Therefore, this study aimed to evaluate the utility of T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) measurements in newborn screening (NBS) for SCID and other primary immunodeficiencies in Kumamoto Prefecture, Japan. In a TREC-based NBS program (February 2019–March 2022, N = 43,658), six newborns (0.014%) underwent immunological testing, and three (0.007%) were diagnosed with T-cell lymphopenia. In a subsequent combined TREC/KREC-based NBS program (April 2022–March 2023, N = 12,335), eight newborns (0.065%) required further testing, and one (0.008%) was diagnosed with X-linked agammaglobulinemia. Decreased KREC levels were observed in two newborns exposed to maternal azathioprine (AZP). The TREC levels tended to be lower in more premature infants, whereas the KREC levels showed no clear correlation with gestational age (GA). Both the TREC and KREC levels were reduced in infants with low birth weights (BWs). These findings indicate that the combined TREC/KREC-based NBS program is an effective approach for detecting T- and B-cell immunodeficiencies. However, clinical factors such as maternal AZP exposure, low GA, and low BW may affect TREC and/or KREC levels, necessitating careful interpretation of results from dried blood spot samples.

The online version contains supplementary material available at 10.1007/s12013-025-01873-5.