Image 2_Pitfalls and diagnostic challenges in TRECS-based newborn screening for Artemis, FOXN1 and Moesin deficiencies.png

However, reduced TRECs levels are a surrogate marker of impaired thymic output rather than a disease-specific finding. Accordingly, low values can result from highly heterogeneous and distinct biological mechanisms of T-cell ontogeny that extend beyond classical SCID phenotypes.

This study describes three patients with inborn errors of immunity (IEI) identified through abnormal TRECs screening who were subsequently diagnosed with Artemis, FOXN1, and Moesin deficiencies. These clinical cases demonstrate that primary T-cell immunodeficiencies can arise from defects at distinct biological levels of T-cell development, specifically in impaired antigen receptor V(D)J recombination (characteristic of NHEJ deficiencies and other SCID conditions), disrupted thymic stromal microenvironment function and compromised peripheral lymphocyte homeostasis, respectively.