Expanded Newborn Screening for Inborn Errors of Immunity: The Experience of Tuscany

Silvia Ricci; Valentina Guarnieri; Francesca Capitanini; Caterina Pelosi; Valeria Astorino; Silvia Boscia; Elisa Calistri; Clementina Canessa; Martina Cortimiglia; Francesca Lippi; Lorenzo Lodi; Sabrina Malvagia; Maria Moriondo; Giancarlo La Marca; Chiara Azzari

doi:10.1016/j.jaip.2024.04.011

Expanded Newborn Screening for Inborn Errors of Immunity: The Experience of Tuscany

J Allergy Clin Immunol Pract. 2024 Apr 16:S2213-2198(24)00395-7. doi: 10.1016/j.jaip.2024.04.011. Online ahead of print.

Authors

Affiliations

¹ Immunology Division, Section of Pediatrics, Meyer Children's Hospital IRCCS, Florence, Italy; Department of Health Sciences, University of Florence, Florence, Italy.
² Department of Health Sciences, University of Florence, Florence, Italy.
³ Immunology Division, Section of Pediatrics, Meyer Children's Hospital IRCCS, Florence, Italy.
⁴ Immunology Division, Section of Pediatrics, Meyer Children's Hospital IRCCS, Florence, Italy; Department of Health Sciences, University of Florence, Florence, Italy. Electronic address: Italylorenzo.lodi@unifi.it.
⁵ Newborn Screening, Clinical Chemistry and Pharmacology Laboratory, Meyer Children's Hospital IRCCS, Florence, Italy; Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.

PMID: 38636590
DOI: 10.1016/j.jaip.2024.04.011

Abstract

Background: Inborn errors of immunity (IEIs) include 485 inherited disorders characterized by an increased susceptibility to life-threatening infectious diseases, autoimmunity, and malignant diseases with a high mortality rate in the first years of life. Severe combined immunodeficiency is the most severe of the IEIs, and its detection should be a primary goal in a newborn screening (NBS) program. The term "actionable" has recently been used for all IEIs with outcomes that can be demonstrably improved through early specialized intervention.

Objective: To evaluate the results of the expanded NBS strategy for IEIs in Tuscany Region (Italy), based on T-cell receptor excision circle, kappa recombining excision circle, and tandem mass-based assays.

Methods: This is a retrospective study collecting data from all infants born in Tuscany from October 10, 2018, to October 10, 2022. Tandem mass assay to identify adenosine deaminase and purine nucleoside phosphorylase deficiency, together with T-cell receptor excision circle and kappa recombining excision circle molecular analysis, was conducted on dried blood spot from the newborns' Guthrie Cards. A new dried blood spot and evaluation by an immunologist were carried out when the results of the first test were outside the diagnostic cutoffs.

Results: A total of 94,319 newborns were evaluated. Referral rates for T-cell recombining excision circles (0.031%) and kappa recombining excision circles (0.074%) in this study are in line with the data available in literature. The results from the expanded NBS strategy revealed an incidence rate of 1 per 9431 affected newborns.

Conclusions: This work represents the first description of a sustainable and real-life-based expanded NBS program for IEIs with a high diagnostic incidence facilitating prompt management of identified patients.

Keywords: ADA; Expanded newborn screening; Inborn errors of immunity; KREC; PNP; TREC.