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Front Immunol. 2017 Nov 6;8:1448. doi: 10.3389/fimmu.2017.01448. eCollection 2017.

First Year of Israeli Newborn Screening for Severe Combined Immunodeficiency-Clinical Achievements and Insights.

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Pediatric Department A and the Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
The National Center for Newborn Screening, Israel Ministry of Health, Tel-HaShomer, Israel.
Pediatric Immunology Clinic, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
The Jeffrey Modell Foundation Israeli Network for Primary Immunodeficiency, New York, NY, United States.
Allergy and Immunology Unit, Schneider Children's Medical Center of Israel, Felsenstein Medical Research Center, Petach Tikva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Ruth Children Hospital, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
Bone Marrow Transplantation Department, Hadassah Hebrew University Medical Center, Hadassah-Hebrew University Medical School, Jerusalem, Israel.
Allergy and Clinical Immunology Clinic, Department of Pediatrics, Shaare Zedek Medical Center, Hadassah-Hebrew University Medical School, Jerusalem, Israel.
Pediatric Allergy Unit, Wolfson Medical Center, Holon, Israel.
Pediatric Department, Wolfson Medical Center, Holon, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
The National Lab for Diagnosing SCID - The Israeli Newborn Screening Program, Israel Ministry of Health, Tel-Hashomer, Israel.


Severe combined immunodeficiency (SCID), the most severe form of T cell immunodeficiency, is detectable through quantification of T cell receptor excision circles (TRECs) in dried blood spots obtained at birth. Herein, we describe the results of the first year of the Israeli SCID newborn screening (NBS) program. This important, life-saving screening test is available at no cost for every newborn in Israel. Eight SCID patients were diagnosed through the NBS program in its first year, revealing an incidence of 1:22,500 births in the Israeli population. Consanguine marriages and Muslim ethnic origin were found to be a risk factor in affected newborns, and a founder effect was detected for both IL7Rα and DCLRE1C deficiency SCID. Lymphocyte subset analysis and TREC quantification in the peripheral blood appear to be sufficient for confirmation of typical and leaky SCID and ruling out false positive (FP) results. Detection of secondary targets (infants with non-SCID lymphopenia) did not significantly affect the management or outcomes of these infants in our cohort. In the general, non-immunodeficient population, TREC rises along with gestational age and birth weight, and is significantly higher in females and the firstborn of twin pairs. Low TREC correlates with both gestational age and birth weight in extremely premature newborns. Additionally, the rate of TREC increase per week consistently accelerates with gestational age. Together, these findings mandate a lower cutoff or a more lenient screening algorithm for extremely premature infants, in order to reduce the high rate of FPs within this group. A significant surge in TREC values was observed between 28 and 30 weeks of gestation, where median TREC copy numbers rise by 50% over 2 weeks. These findings suggest a maturational step in T cell development around week 29 gestation, and imply moderate to late preterms should be screened with the same cutoff as term infants. The SCID NBS program is still in its infancy, but is already bearing fruit in the early detection and improved outcomes of children with SCID in Israel and other countries.


T cell development; immunodeficiency; newborn screening; preterm; severe combined immunodeficiency

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