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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02406

First Universal Newborn Screening Program for Severe Combined Immunodeficiency in Europe. Two-years’ Experience in Catalonia (Spain)

 Ana Argudo-Ramírez1, 2, Andrea Martín-Nalda3, Jose Luis Marín-Soria2, Rosa María López-Galera2,  Sonia Pajares-García2, Jose Manuel González de Aledo-Castillo2,  Mónica Martínez-Gallo4, Marina García-Prat3, Roger Colobran4, 5, Jacques G. Rivière3, Yania Quintero2, Tatiana Collado2, Judit García-Villoria2, Antonia Ribes2 and  Pere Soler-Palacín3*
  • 1Hospital Clínic de Barcelona, Spain
  • 2Section of Inborn Errors of Metabolism, Biochemistry and Molecular Genetics Laboratory, Hospital Clinic of Barcelona, Spain
  • 3Division of Infectious Diseases and Pediatric Immunology, Department of Pediatrics, Vall d'Hebron University Hospital, Spain
  • 4Division of Immunology, Vall d'Hebron University Hospital, Spain
  • 5Department of Clinical and Molecular Genetics, Hospital Universitari Vall d’Hebron, Spain

Severe combined immunodeficiency (SCID), the most severe form of T-cell immunodeficiency, can be screened at birth by quantifying T-cell receptor excision circles (TRECs) in dried blood spot (DBS) samples. Early detection of this condition speeds up establishment of appropriate treatment and increases the patient’s life expectancy. Newborn screening for SCID started in January 2017 in Catalonia, the first Spanish and European region to universally include this testing. The results obtained in the first 2 years of experience are evaluated here. All babies born between January 2017 and December 2018 were screened. TREC quantification in DBS (1.5 mm diameter) was performed with the Enlite Neonatal TREC kit from PerkinElmer (Turku, Finland). In 2018, the retest cutoff in the detection algorithm was updated based on the first year’s experience, and changed from 34 to 24 copies/µL. This decreased the retest rate from 3.34% to 1.4% (global retest rate, 2.4%), with a requested second sample rate of 0.23% and a positive detection rate of 0.02%. Lymphocyte phenotype (T, B, NK populations), expression of CD45RA/RO isoforms, percentage and intensity of TCR αβ and TCR γδ, presence of HLA-DR+ T lymphocytes, and in vitro lymphocyte proliferation were studied in all patients by flow cytometry. Of 130,903 newborns screened, 30 tested positive and 15 were males. During the study period, 1 patient was diagnosed with SCID: incidence, 1 in 130,903 births in Catalonia. Thirteen patients had clinically significant T-cell lymphopenia (non-SCID) with an incidence of 1 in 10,069 newborns (43% of positive detections). Nine patients were considered false-positive cases because of an initially normal lymphocyte count with normalization of TRECs between 3 and 6 months of life, 4 infants had transient lymphopenia due to an initially low lymphocyte count with recovery in the following months, and 3 patients are still under study. The results obtained provide further evidence of the benefits of including this disease in newborn screening programs. Longer follow-up is needed to define the exact incidence of SCID in Catalonia.

Keywords: Newborn screening, Severe combined immunodeficiency (SCID), T-cell receptor excision circles (TRECs), T-cell receptor (TCR), T-Lymphocytes, Stem Cell Transplantation (HSCT)

Received: 27 May 2019; Accepted: 25 Sep 2019.

Copyright: © 2019 Argudo-Ramírez, Martín-Nalda, Marín-Soria, López-Galera, Pajares-García, González de Aledo-Castillo, Martínez-Gallo, García-Prat, Colobran, Rivière, Quintero, Collado, García-Villoria, Ribes and Soler-Palacín. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: MD, PhD. Pere Soler-Palacín, Division of Infectious Diseases and Pediatric Immunology, Department of Pediatrics, Vall d'Hebron University Hospital, Barcelona, Catalonia, Spain, psoler@vhebron.net