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Immunological Findings and Clinical Outcomes of Infants With Positive Newborn Screening for Severe Combined Immunodeficiency From a Tertiary Care Center in the U.S.

The implementation of severe combined immunodeficiency (SCID) newborn screening has played a pivotal role in identifying these patients early in life as well as detecting various milder forms of T cell lymphopenia (TCL). In this study we reviewed the diagnostic and clinical outcomes, and interesting...

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Autores principales: Mantravadi, Vasudha, Bednarski, Jeffrey J., Ritter, Michelle A., Gu, Hongjie, Kolicheski, Ana L., Horner, Caroline, Cooper, Megan A., Kitcharoensakkul, Maleewan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446381/
https://www.ncbi.nlm.nih.gov/pubmed/34539671
http://dx.doi.org/10.3389/fimmu.2021.734096
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author Mantravadi, Vasudha
Bednarski, Jeffrey J.
Ritter, Michelle A.
Gu, Hongjie
Kolicheski, Ana L.
Horner, Caroline
Cooper, Megan A.
Kitcharoensakkul, Maleewan
author_facet Mantravadi, Vasudha
Bednarski, Jeffrey J.
Ritter, Michelle A.
Gu, Hongjie
Kolicheski, Ana L.
Horner, Caroline
Cooper, Megan A.
Kitcharoensakkul, Maleewan
author_sort Mantravadi, Vasudha
collection PubMed
description The implementation of severe combined immunodeficiency (SCID) newborn screening has played a pivotal role in identifying these patients early in life as well as detecting various milder forms of T cell lymphopenia (TCL). In this study we reviewed the diagnostic and clinical outcomes, and interesting immunology findings of term infants referred to a tertiary care center with abnormal newborn SCID screens over a 6-year period. Key findings included a 33% incidence of non-SCID TCL including infants with novel variants in FOXN1, TBX1, MYSM1, POLD1, and CD3E; 57% positivity rate of newborn SCID screening among infants with DiGeorge syndrome; and earlier diagnosis and improved transplant outcomes for SCID in infants diagnosed after compared to before implementation of routine screening. Our study is unique in terms of the extensive laboratory workup of abnormal SCID screens including lymphocyte subsets, measurement of thymic output (TREC and CD4TE), and lymphocyte proliferation to mitogens in nearly all infants. These data allowed us to observe a stronger positive correlation of the absolute CD3 count with CD4RTE than with TREC copies, and a weak positive correlation between CD4RTE and TREC copies. Finally, we did not observe a correlation between risk of TCL and history of prenatal or perinatal complications or low birth weight. Our study demonstrated SCID newborn screening improves disease outcomes, particularly in typical SCID, and allows early detection and discovery of novel variants of certain TCL-associated genetic conditions.
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spelling pubmed-84463812021-09-18 Immunological Findings and Clinical Outcomes of Infants With Positive Newborn Screening for Severe Combined Immunodeficiency From a Tertiary Care Center in the U.S. Mantravadi, Vasudha Bednarski, Jeffrey J. Ritter, Michelle A. Gu, Hongjie Kolicheski, Ana L. Horner, Caroline Cooper, Megan A. Kitcharoensakkul, Maleewan Front Immunol Immunology The implementation of severe combined immunodeficiency (SCID) newborn screening has played a pivotal role in identifying these patients early in life as well as detecting various milder forms of T cell lymphopenia (TCL). In this study we reviewed the diagnostic and clinical outcomes, and interesting immunology findings of term infants referred to a tertiary care center with abnormal newborn SCID screens over a 6-year period. Key findings included a 33% incidence of non-SCID TCL including infants with novel variants in FOXN1, TBX1, MYSM1, POLD1, and CD3E; 57% positivity rate of newborn SCID screening among infants with DiGeorge syndrome; and earlier diagnosis and improved transplant outcomes for SCID in infants diagnosed after compared to before implementation of routine screening. Our study is unique in terms of the extensive laboratory workup of abnormal SCID screens including lymphocyte subsets, measurement of thymic output (TREC and CD4TE), and lymphocyte proliferation to mitogens in nearly all infants. These data allowed us to observe a stronger positive correlation of the absolute CD3 count with CD4RTE than with TREC copies, and a weak positive correlation between CD4RTE and TREC copies. Finally, we did not observe a correlation between risk of TCL and history of prenatal or perinatal complications or low birth weight. Our study demonstrated SCID newborn screening improves disease outcomes, particularly in typical SCID, and allows early detection and discovery of novel variants of certain TCL-associated genetic conditions. Frontiers Media S.A. 2021-09-03 /pmc/articles/PMC8446381/ /pubmed/34539671 http://dx.doi.org/10.3389/fimmu.2021.734096 Text en Copyright © 2021 Mantravadi, Bednarski, Ritter, Gu, Kolicheski, Horner, Cooper and Kitcharoensakkul https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Immunology
Mantravadi, Vasudha
Bednarski, Jeffrey J.
Ritter, Michelle A.
Gu, Hongjie
Kolicheski, Ana L.
Horner, Caroline
Cooper, Megan A.
Kitcharoensakkul, Maleewan
Immunological Findings and Clinical Outcomes of Infants With Positive Newborn Screening for Severe Combined Immunodeficiency From a Tertiary Care Center in the U.S.
title Immunological Findings and Clinical Outcomes of Infants With Positive Newborn Screening for Severe Combined Immunodeficiency From a Tertiary Care Center in the U.S.
title_full Immunological Findings and Clinical Outcomes of Infants With Positive Newborn Screening for Severe Combined Immunodeficiency From a Tertiary Care Center in the U.S.
title_fullStr Immunological Findings and Clinical Outcomes of Infants With Positive Newborn Screening for Severe Combined Immunodeficiency From a Tertiary Care Center in the U.S.
title_full_unstemmed Immunological Findings and Clinical Outcomes of Infants With Positive Newborn Screening for Severe Combined Immunodeficiency From a Tertiary Care Center in the U.S.
title_short Immunological Findings and Clinical Outcomes of Infants With Positive Newborn Screening for Severe Combined Immunodeficiency From a Tertiary Care Center in the U.S.
title_sort immunological findings and clinical outcomes of infants with positive newborn screening for severe combined immunodeficiency from a tertiary care center in the u.s.
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446381/
https://www.ncbi.nlm.nih.gov/pubmed/34539671
http://dx.doi.org/10.3389/fimmu.2021.734096
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