Determining the Number of TREC and KREC Copies for Screening of Inborn Errors of Immunity

T-cell receptor excision circles (TRECs) and kappa-deleting recombinant excision circles (KRECs) are circular DNA molecules that are formed in the process of maturation of T and B cells of the human immune response and can be markers of the development and number of the immune response cells. The authors determined the number of TREC and KREC copies in different biological material and their informativeness for screening patients with inborn errors of immunity. The number of TREC and KREC molecules was determined using a real-time polymerase chain reaction followed by the analysis of melting curves in the material of neonatal dry spots and DNA bank of patients with inborn errors of immunity. The determination of the number of copies of TREC molecules reveals 100% sensitivity for the detection of Nijmegen breakage syndrome and 84% for ataxia–telangiectasia. The determination of KREC index demonstrated a significantly lower sensitivity (56 and 37%, respectively). The calculations carried out when performing 1500 tests indicate an index of TREC determination specificity at the level of 97.6% for the first blood spot and 97.3% after the repeated sampling. Performing this study on a large sample of healthy newborns (more than 10 000) should be the next stage of the work in order to establish the limit values for the number of TREC and KREC copies in our population. The determination of TREC and KREC copies is a rapid and accessible method and can be suitable for use in screening programs provided that the results obtained are replicated on a larger sample. The determination of the number of TREC copies using the proposed method demonstrated the sensitivity of 93.6% and specificity of 97.3% for detecting the cases of inborn errors of immunity accompanied by T lymphopenia.