Clin Exp Pediatr.  2021 Oct;64(10):504-510. 10.3345/cep.2020.01270.

Modern diagnostic capabilities of neonatal screening for primary immunodeficiencies in newborns

• Khalturina EO
• Degtyareva ND
• Bairashevskaia AV
• Mulenkova AV
• Degtyareva AV

• KMID: 2520826
• DOI: http://doi.org/10.3345/cep.2020.01270

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 coinfections of a viral-bacterial-fungal etiology. Modern advances in medical laboratory technology have allowed the identification of children with severe PIDS, manifested by T- and/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 kappa-recombination excision circles, as well as the potential role and place of next-generation sequencing technology to increase the diagnostic accuracy of these diseases.

Keyword

Neonatal screening; Primary immunodeficiency syndromes; Sequencing; T-cell receptors excision circle; Kappa-recombination excision circle; Next-generation sequencing