Implementation of TREC/KREC detection protocol for newborn SCID screening in Bulgaria: a pilot study

Abstract

Neonatal screening for inborn errors of immunity (IEI), based on quantification of T-cell-receptor- excision circles (TRECs) and kappa-deleting recombination-excision circles (KRECs) from dried blood spots (DBS), allows early diagnosis and improved outcomes for the affected children. Determination of TREC/KREC levels from prospectively collected newborns’ Guthrie cards and from DBS samples of patients with confirmed IEI was done using a commercial kit. Retrospective assessment of flow cytometry evaluation of TREC/KREC correspondence with lymphocyte subpopulations and evaluation of the correlations between TREC and KREC with immune cells, based on the data from patients with suspected or confirmed immune disorders, were conducted. 2,228 Guthrie cards were tested, 1276 for TREC only and 952 for both TREC and KREC. Eight newborns (0.36%) were TREC positive and 10 (1.05%) had KREC below the cut-off. The re-testing rate was 1.88%. Retrospective analysis demonstrated that the TREC/KREC assay identifies 100% of severe combined immune deficiencies (SCID) cases when DBS were collected at birth. Correlation analysis showed moderate significant correlations between TREC and the absolute numbers of CD4 cells (r = 0.634, p < 0.01) and total T cells (r = 0.536, p < 0.01). The ability of KREC levels to predict abnormal absolute (AUC of 0.772) and relative (AUC 0.731) levels of B cells was demonstrated.

Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020–2023)

“…Both pediatricians and geneticists considered selective WGS as a potential option for improving Bulgarian NBS [ 728 ]. The results of a pilot study demonstrating the feasibility of SCID screening were recently reported [ 729 ]. Cases of arginase deficiency in the Roma area point to the need for ARG screening in this region [ 730 ].…”

Immunodeficiency Disorders in Congenital Heart Diseases (Review)

“…При заболеваниях с В-клеточным иммунодефицитом (Х-сцепленная агаммаглобулинемия и общий вариабельный иммунодефицит) высокочувствительны и специфичны показатели KREC, а при аутоиммунных заболеваниях значения KREC коррелируют с активностью процесса и ответом на терапию [58,59].…”

“…Эти маркеры стали важными -быстрыми, простыми, неинвазивными и относительно недорогими -современными высокочувствительными и специфичными компонентами комплексного неонатального скрининга в составе других тестов и маркеров широкого спектра генетических и метаболических нарушений. Измерение TREC и KREC позволяет проводить скрининг большого числа новорожденных за короткий промежуток времени [53,[59][60][61][62][63][64][65].…”