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Newborn Screening for Severe Primary Immunodeficiency Diseases in Sweden—a 2-Year Pilot TREC and KREC Screening Study

Newborn screening for severe primary immunodeficiencies (PID), characterized by T and/or B cell lymphopenia, was carried out in a pilot program in the Stockholm County, Sweden, over a 2-year period, encompassing 58,834 children. T cell receptor excision circles (TREC) and kappa-deleting recombinatio...

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Autores principales: Barbaro, Michela, Ohlsson, Annika, Borte, Stephan, Jonsson, Susanne, Zetterström, Rolf H., King, Jovanka, Winiarski, Jacek, von Döbeln, Ulrika, Hammarström, Lennart
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226987/
https://www.ncbi.nlm.nih.gov/pubmed/27873105
http://dx.doi.org/10.1007/s10875-016-0347-5
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author Barbaro, Michela
Ohlsson, Annika
Borte, Stephan
Jonsson, Susanne
Zetterström, Rolf H.
King, Jovanka
Winiarski, Jacek
von Döbeln, Ulrika
Hammarström, Lennart
author_facet Barbaro, Michela
Ohlsson, Annika
Borte, Stephan
Jonsson, Susanne
Zetterström, Rolf H.
King, Jovanka
Winiarski, Jacek
von Döbeln, Ulrika
Hammarström, Lennart
author_sort Barbaro, Michela
collection PubMed
description Newborn screening for severe primary immunodeficiencies (PID), characterized by T and/or B cell lymphopenia, was carried out in a pilot program in the Stockholm County, Sweden, over a 2-year period, encompassing 58,834 children. T cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) were measured simultaneously using a quantitative PCR-based method on DNA extracted from dried blood spots (DBS), with beta-actin serving as a quality control for DNA quantity. Diagnostic cutoff levels enabling identification of newborns with milder and reversible T and/or B cell lymphopenia were also evaluated. Sixty-four children were recalled for follow-up due to low TREC and/or KREC levels, and three patients with immunodeficiency (Artemis-SCID, ATM, and an as yet unclassified T cell lymphopenia/hypogammaglobulinemia) were identified. Of the positive samples, 24 were associated with prematurity. Thirteen children born to mothers treated with immunosuppressive agents during pregnancy (azathioprine (n = 9), mercaptopurine (n = 1), azathioprine and tacrolimus (n = 3)) showed low KREC levels at birth, which spontaneously normalized. Twenty-nine newborns had no apparent cause identified for their abnormal results, but normalized with time. Children with trisomy 21 (n = 43) showed a lower median number of both TREC (104 vs. 174 copies/μL blood) and KREC (45 vs. 100 copies/3.2 mm blood spot), but only one, born prematurely, fell below the cutoff level. Two children diagnosed with DiGeorge syndrome were found to have low TREC levels, but these were still above the cutoff level. This is the first large-scale screening study with a simultaneous detection of both TREC and KREC, allowing identification of newborns with both T and B cell defects. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10875-016-0347-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-52269872017-01-24 Newborn Screening for Severe Primary Immunodeficiency Diseases in Sweden—a 2-Year Pilot TREC and KREC Screening Study Barbaro, Michela Ohlsson, Annika Borte, Stephan Jonsson, Susanne Zetterström, Rolf H. King, Jovanka Winiarski, Jacek von Döbeln, Ulrika Hammarström, Lennart J Clin Immunol Original Article Newborn screening for severe primary immunodeficiencies (PID), characterized by T and/or B cell lymphopenia, was carried out in a pilot program in the Stockholm County, Sweden, over a 2-year period, encompassing 58,834 children. T cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) were measured simultaneously using a quantitative PCR-based method on DNA extracted from dried blood spots (DBS), with beta-actin serving as a quality control for DNA quantity. Diagnostic cutoff levels enabling identification of newborns with milder and reversible T and/or B cell lymphopenia were also evaluated. Sixty-four children were recalled for follow-up due to low TREC and/or KREC levels, and three patients with immunodeficiency (Artemis-SCID, ATM, and an as yet unclassified T cell lymphopenia/hypogammaglobulinemia) were identified. Of the positive samples, 24 were associated with prematurity. Thirteen children born to mothers treated with immunosuppressive agents during pregnancy (azathioprine (n = 9), mercaptopurine (n = 1), azathioprine and tacrolimus (n = 3)) showed low KREC levels at birth, which spontaneously normalized. Twenty-nine newborns had no apparent cause identified for their abnormal results, but normalized with time. Children with trisomy 21 (n = 43) showed a lower median number of both TREC (104 vs. 174 copies/μL blood) and KREC (45 vs. 100 copies/3.2 mm blood spot), but only one, born prematurely, fell below the cutoff level. Two children diagnosed with DiGeorge syndrome were found to have low TREC levels, but these were still above the cutoff level. This is the first large-scale screening study with a simultaneous detection of both TREC and KREC, allowing identification of newborns with both T and B cell defects. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10875-016-0347-5) contains supplementary material, which is available to authorized users. Springer US 2016-11-21 2017 /pmc/articles/PMC5226987/ /pubmed/27873105 http://dx.doi.org/10.1007/s10875-016-0347-5 Text en © The Author(s) 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Barbaro, Michela
Ohlsson, Annika
Borte, Stephan
Jonsson, Susanne
Zetterström, Rolf H.
King, Jovanka
Winiarski, Jacek
von Döbeln, Ulrika
Hammarström, Lennart
Newborn Screening for Severe Primary Immunodeficiency Diseases in Sweden—a 2-Year Pilot TREC and KREC Screening Study
title Newborn Screening for Severe Primary Immunodeficiency Diseases in Sweden—a 2-Year Pilot TREC and KREC Screening Study
title_full Newborn Screening for Severe Primary Immunodeficiency Diseases in Sweden—a 2-Year Pilot TREC and KREC Screening Study
title_fullStr Newborn Screening for Severe Primary Immunodeficiency Diseases in Sweden—a 2-Year Pilot TREC and KREC Screening Study
title_full_unstemmed Newborn Screening for Severe Primary Immunodeficiency Diseases in Sweden—a 2-Year Pilot TREC and KREC Screening Study
title_short Newborn Screening for Severe Primary Immunodeficiency Diseases in Sweden—a 2-Year Pilot TREC and KREC Screening Study
title_sort newborn screening for severe primary immunodeficiency diseases in sweden—a 2-year pilot trec and krec screening study
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226987/
https://www.ncbi.nlm.nih.gov/pubmed/27873105
http://dx.doi.org/10.1007/s10875-016-0347-5
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