Impact of newborn screening for SCID on the management of congenital athymia.

DiGeorge syndrome Thymus transplantation athymia newborn screening severe combined immunodeficiency

Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
09 Sep 2023
Historique:
received: 11 06 2023
revised: 29 08 2023
accepted: 31 08 2023
pubmed: 8 9 2023
medline: 8 9 2023
entrez: 7 9 2023
Statut: aheadofprint

Résumé

Newborn screening (NBS) programs for severe combined immunodeficiency facilitate early diagnosis of severe combined immunodeficiency and promote early treatment with hematopoietic stem cell transplantation, resulting in improved clinical outcomes. Infants with congenital athymia are also identified through NBS because of severe T-cell lymphopenia. With the expanding introduction of NBS programs, referrals of athymic patients for treatment with thymus transplantation have recently increased at Great Ormond Street Hospital (GOSH) (London, United Kingdom). We studied the impact of NBS on timely diagnosis and treatment of athymic infants with thymus transplantation at GOSH. We compared age at referral and complications between athymic infants diagnosed after clinical presentation (n = 25) and infants identified through NBS (n = 19) who were referred for thymus transplantation at GOSH between October 2019 and February 2023. We assessed whether age at time of treatment influences thymic output at 6 and 12 months after transplantation. The infants referred after identification through NBS were significantly younger and had fewer complications, in particular fewer infections. All deaths occurred in the group of those who did not undergo NBS, including 6 patients before and 2 after thymus transplantation because of preexisting infections. In the absence of significant comorbidities or diagnostic uncertainties, timely treatment was achieved more frequently after NBS. Treatment when younger than age 4 months was associated with higher thymic output at 6 and 12 months after transplantation. NBS contributes to earlier recognition of congenital athymia, promoting referral of athymic patients for thymus transplantation before they acquire infections or other complications and facilitating treatment at a younger age, thus playing an important role in improving their outcomes.

Sections du résumé

BACKGROUND BACKGROUND
Newborn screening (NBS) programs for severe combined immunodeficiency facilitate early diagnosis of severe combined immunodeficiency and promote early treatment with hematopoietic stem cell transplantation, resulting in improved clinical outcomes. Infants with congenital athymia are also identified through NBS because of severe T-cell lymphopenia. With the expanding introduction of NBS programs, referrals of athymic patients for treatment with thymus transplantation have recently increased at Great Ormond Street Hospital (GOSH) (London, United Kingdom).
OBJECTIVE OBJECTIVE
We studied the impact of NBS on timely diagnosis and treatment of athymic infants with thymus transplantation at GOSH.
METHODS METHODS
We compared age at referral and complications between athymic infants diagnosed after clinical presentation (n = 25) and infants identified through NBS (n = 19) who were referred for thymus transplantation at GOSH between October 2019 and February 2023. We assessed whether age at time of treatment influences thymic output at 6 and 12 months after transplantation.
RESULTS RESULTS
The infants referred after identification through NBS were significantly younger and had fewer complications, in particular fewer infections. All deaths occurred in the group of those who did not undergo NBS, including 6 patients before and 2 after thymus transplantation because of preexisting infections. In the absence of significant comorbidities or diagnostic uncertainties, timely treatment was achieved more frequently after NBS. Treatment when younger than age 4 months was associated with higher thymic output at 6 and 12 months after transplantation.
CONCLUSION CONCLUSIONS
NBS contributes to earlier recognition of congenital athymia, promoting referral of athymic patients for thymus transplantation before they acquire infections or other complications and facilitating treatment at a younger age, thus playing an important role in improving their outcomes.

Identifiants

DOI: 10.1016/j.jaci.2023.08.031 PMID: 37678573
pubmed: 37678573
pii: S0091-6749(23)01114-4
doi: 10.1016/j.jaci.2023.08.031
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Evey Howley (E)

Department of Immunology and Gene Therapy, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.

Zainab Golwala (Z)

Department of Immunology and Gene Therapy, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.

Matthew Buckland (M)

Department of Immunology and Gene Therapy, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.

Federica Barzaghi (F)

San Raffaele Telethon Institute for Gene Therapy and Pediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Sujal Ghosh (S)

Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-University, Düsseldorf, Germany.

Scott Hackett (S)

University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.

Rosie Hague (R)

Department of Paediatric Infectious Diseases and Immunology, Royal Hospital for Children, Glasgow, United Kingdom.

Fabian Hauck (F)

Department of Pediatrics, Dr von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Ursula Holzer (U)

University Children's Hospital, Eberhard Karls University, Tübingen, Germany.

Adam Klocperk (A)

Department of Immunology, Second Faculty of Medicine, Charles University and University Hospital in Motol, Prague, Israel.

Minna Koskenvuo (M)

Division of Hematology-Oncology and Stem Cell Transplantation, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Nufar Marcus (N)

Kipper Institute for Immunology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Antonio Marzollo (A)

Pediatric Hematology, Oncology and Stem Cell Transplant Division, Padua University Hospital, Padua, Italy.

Malgorzata Pac (M)

Department of Immunology, Children's Memorial Health Institute, Warsaw, Poland.

Jan Sinclair (J)

Starship Children's Hospital, Auckland, New Zealand.

Carsten Speckmann (C)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Faculty of Medicine, Faculty of Medicine, Medical Center-University of Freiburg, Germany; Center for Pediatrics and Adolescent Medicine, Department of Pediatric Hematology and Oncology, Faculty of Medicine, Medical Center-University of Freiburg, Germany.

Maarja Soomann (M)

Division of Immunology, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.

Lynne Speirs (L)

Department of Paediatrics, Royal Belfast Hospital for Sick Children, Belfast, United Kingdom.

Sneha Suresh (S)

Division of IHOPE, Department of Pediatrics, University of Alberta, Edmonton, Canada.

Sophie Taque (S)

Department of Paediatrics, CHU Rennes, Rennes, France.

Joris van Montfrans (J)

Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands.

Horst von Bernuth (H)

Department of Pediatric Respiratory Medicine, Immunology, and Critical Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany; Labor Berlin Charité-Vivantes, Department of Immunology, Berlin, Germany; Berlin Institute of Health, Charité Universitätsmedizin Berlin, Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany.

Brynn K Wainstein (BK)

Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Sydney, Australia; School of Clinical Medicine, University of New South Wales, Sydney, Australia.

Austen Worth (A)

Department of Immunology and Gene Therapy, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.

E Graham Davies (EG)

Department of Immunology and Gene Therapy, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; Infection, Immunity and Inflammation Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.

Alexandra Y Kreins (AY)

Department of Immunology and Gene Therapy, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; Infection, Immunity and Inflammation Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, London, United Kingdom. Electronic address: a.kreins@ucl.ac.uk.

Classifications MeSH