TREC and KREC concentration in the screening of inborn errors of immunity

BACKGROUND: The lack of accessible screening for inborn errors of immunity in adults significantly complicates the diagnosis of these conditions. In more than half of the cases, this leads to delayed disease detection and the development of irreversible complications in patients.

AIM: To determine reference intervals for TREC and KREC concentrations in adults and evaluate the possibility of their use for inborn errors of immunity screening using the “NeoScreen SMA/TREC/KREC” test system.

METHODS: A single-center observational cross-sectional controlled non-randomized study was conducted involving 101 patients. The study included groups with humoral and combined immune defects, divided into subgroups with predominant humoral immune defects (antibody synthesis disorders) and combined immune defects, as well as a control group of conditionally healthy participants. TREC and KREC levels were determined using polymerase chain reaction. The study was conducted from September 2024 to August 2025. Statistical analysis included group comparisons (Mann–Whitney and Kruskal–Wallis tests), ROC analysis. Reference intervals were determined using the direct method according to International Federation of Clinical Chemistry and Laboratory Medicine recommendations. Statistical significance was confirmed at p < 0,05.

RESULTS: The study included 101 participants: 46 patients in the control group and 55 patients with inborn errors of immunity. Statistically significant differences in TREC and KREC levels were observed between healthy participants under 39 years and over 40 years (p < 0,001 and p = 0,003, respectively). Subgroup analysis showed: in the humoral immune defects subgroup, KREC levels demonstrated area under curve — 0,87, specificity — 95 %, sensitivity — 68 %. In the subgroup with combined immune defects, the method did not show statistically significant differences with the control group when comparing TREC and KREC levels (p = 0,639 and p = 0,092, respectively).

CONCLUSION: The development of separate threshold values for patients over 40 years of age is required. The method is effective for screening humoral immune disorders but is not suitable for combined forms of inborn errors of immunity. Despite the high specificity and sensitivity of KREC as a diagnostic marker, the method cannot be recommended as a replacement for existing diagnostic methods due to the availability of more accessible and effective screening approaches.