Modern diagnostic capabilities of neonatal screening for primary immunodeficiencies in newborns

Abstract

Population screening of newborns is an extremely important and informative diagnostic approach that allows early identification of babies who are predisposed to the development of a number of serious diseases. Some of these diseases are known and have effective treatment methods. Neonatal screening enables the early diagnosis and subsequent timely initiation of therapy. This helps to prevent serious complications and reduce the percentage of disability and deaths among newborns and young children. Primary immunodeficiency diseases and primary immunodeficiency syndrome (PIDS) are a heterogeneous group of diseases and conditions based on impaired immune system function associated with developmental defects and characterized by various combinations of recurrent infections, development of autoimmune and lymphoproliferative syndromes (genetic defects in apoptosis, gene mutation Fas receptor or ligand), granulomatous process, and malignant neoplasms. Most of these diseases manifest in infancy and lead to serious illness, disability, and high mortality rates. Until recently, it was impossible to identify children with PIDS before the onset of the first clinical symptoms, which are usually accompanied by complications in the form of severe co-infections of a viral-bacterial-fungal etiology. Modern advances in medical laboratory technology have allowed the identification of children with severe PIDS, manifested by Tand/or B-cell lymphopenia and other disorders of the immune system. This review discusses the main existing strategies and directions used in PIDS screening programs for newborns, including approaches to screening based on excision of T-cell receptors and kapparecombination excision circles, as well as the potential role and place of next-generation sequencing technology to increase the diagnostic accuracy of these diseases.

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

“…A 2017 review of the past, present, and future of pediatrics in Russia helps to better understand national pediatric healthcare issues [ 978 ]. In preparation for the expansion, three SCID-related studies were published: two reviews of TREC and KREC screening, including the potential role of NGS in increasing the diagnostic accuracy of PIDS in general [ 979 , 980 ]; and determination of the 95% confidence intervals for TREC and KREC levels for different gestational groups with the suggestion that gestational age is an important factor that affects both TREC and KREC levels in newborns [ 981 ]. A recent publication reported on a pilot project for SMA NBS in St. Petersburg, which identified cases and supported the idea of earlier detection and diagnosis through NBS [ 982 ].…”

High diagnostic rate of whole genome sequencing in primary ciliary dyskinesia

“…Increasing availability, reducing costs and recognised clinical utility of NGS platforms such as WGS in the neonatal and paediatric intensive care unit setting would be consistent with such indications (50,51,54,56–59). Moreover, either WES or WGS would help rule out other confounding clinical presentations such as primary immune deficiency disorders (PIDs), with overlapping symptoms of frequent, often severe, airway infections as well as recurrent otitis media, and sinusitis (60–62). Both platforms are advantageous as they allow analysis of all potential causative genes, known and novel, thus faster to keep up with recently reported genes that may not yet be included on PCD-gene panels.…”