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Long-Term Follow-Up of Newborns with 22q11 Deletion Syndrome and Low TRECs

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dc.contributor Landspitali - The National University Hospital of Iceland
dc.contributor.author Framme, Jenny Lingman
dc.contributor.author Lundqvist, Christina
dc.contributor.author Lundell, Anna Carin
dc.contributor.author van Schouwenburg, Pauline A.
dc.contributor.author Lemarquis, Andri L.
dc.contributor.author Thörn, Karolina
dc.contributor.author Lindgren, Susanne
dc.contributor.author Gudmundsdottir, Judith
dc.contributor.author Lundberg, Vanja
dc.contributor.author Degerman, Sofie
dc.contributor.author Zetterström, Rolf H.
dc.contributor.author Borte, Stephan
dc.contributor.author Hammarström, Lennart
dc.contributor.author Telemo, Esbjörn
dc.contributor.author Hultdin, Magnus
dc.contributor.author van der Burg, Mirjam
dc.contributor.author Fasth, Anders
dc.contributor.author Oskarsdóttir, Sólveig
dc.contributor.author Ekwall, Olov
dc.date.accessioned 2022-04-05T01:02:42Z
dc.date.available 2022-04-05T01:02:42Z
dc.date.issued 2022-01-26
dc.identifier.citation Framme , J L , Lundqvist , C , Lundell , A C , van Schouwenburg , P A , Lemarquis , A L , Thörn , K , Lindgren , S , Gudmundsdottir , J , Lundberg , V , Degerman , S , Zetterström , R H , Borte , S , Hammarström , L , Telemo , E , Hultdin , M , van der Burg , M , Fasth , A , Oskarsdóttir , S & Ekwall , O 2022 , ' Long-Term Follow-Up of Newborns with 22q11 Deletion Syndrome and Low TRECs ' , Journal of Clinical Immunology , vol. 42 , no. 3 , pp. 618-633 . https://doi.org/10.1007/s10875-021-01201-5
dc.identifier.issn 0271-9142
dc.identifier.other PURE: 46783948
dc.identifier.other PURE UUID: dbf2bf52-1807-4673-a1bc-8e6dccac0202
dc.identifier.other Scopus: 85123620385
dc.identifier.other researchoutputwizard: hdl.handle.net/2336/622116
dc.identifier.other unpaywall: 10.1007/s10875-021-01201-5
dc.identifier.uri https://hdl.handle.net/20.500.11815/3018
dc.description Funding Information: The authors thank the study participants and their families for their contributions to this study. We are indebted to the staff at Queen Silvia Children´s Hospital, Gothenburg, Halland Hospital Halmstad, and the Clinical Immunology Laboratory at Sahlgrenska University Hospital, Gothenburg, especially nurses Jeanette Nyström and Louise Alexandersson. We also thank Pia Osterman for laboratory assistance and Mattias Landfors for support with statistics. Funding Information: Open access funding provided by University of Gothenburg. This study is funded by Regional research grant, Region Halland, The Swedish Research Council [grant number 2018-02752], Queen Silvia Jubilee Foundation, Swedish Primary Immunodeficiency Organization, Regional research grant, Sparbanken Foundation, Varberg, Region Halland, Frimurare Barnhusdirektionen Foundation, The Gothenburg Medical Society, Medical Faculty at Umeå University, and Cancer Research Foundation in Northern Sweden [grant number AMP 20-1000]. The study was also financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement [grant numbers ALFGBG-717431, 718021]. Financial support was also provided through a regional agreement between Umeå University and Västerbottens County Council on cooperation in the field of Medicine, Odontology, and Health [grant numbers RV-932787, RV-939741]. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2022, The Author(s).
dc.description.abstract Background: Population-based neonatal screening using T-cell receptor excision circles (TRECs) identifies infants with profound T lymphopenia, as seen in cases of severe combined immunodeficiency, and in a subgroup of infants with 22q11 deletion syndrome (22q11DS). Purpose: To investigate the long-term prognostic value of low levels of TRECs in newborns with 22q11DS. Methods: Subjects with 22q11DS and low TRECs at birth (22q11Low, N=10), matched subjects with 22q11DS and normal TRECs (22q11Normal, N=10), and matched healthy controls (HC, N=10) were identified. At follow-up (median age 16 years), clinical and immunological characterizations, covering lymphocyte subsets, immunoglobulins, TRECs, T-cell receptor repertoires, and relative telomere length (RTL) measurements were performed. Results: At follow-up, the 22q11Low group had lower numbers of naïve T-helper cells, naïve T-regulatory cells, naïve cytotoxic T cells, and persistently lower TRECs compared to healthy controls. Receptor repertoires showed skewed V-gene usage for naïve T-helper cells, whereas for naïve cytotoxic T cells, shorter RTL and a trend towards higher clonality were found. Multivariate discriminant analysis revealed a clear distinction between the three groups and a skewing towards Th17 differentiation of T-helper cells, particularly in the 22q11Low individuals. Perturbations of B-cell subsets were found in both the 22q11Low and 22q11Normal group compared to the HC group, with larger proportions of naïve B cells and lower levels of memory B cells, including switched memory B cells. Conclusions: This long-term follow-up study shows that 22q11Low individuals have persistent immunologic aberrations and increased risk for immune dysregulation, indicating the necessity of lifelong monitoring. Clinical Implications: This study elucidates the natural history of childhood immune function in newborns with 22q11DS and low TRECs, which may facilitate the development of programs for long-term monitoring and therapeutic choices.
dc.format.extent 16
dc.format.extent 618-633
dc.language.iso en
dc.relation.ispartofseries Journal of Clinical Immunology; 42(3)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Barnalæknisfræði
dc.subject 22q11.2 deletion syndrome
dc.subject DiGeorge syndrome
dc.subject T lymphopenia
dc.subject TREC
dc.subject long-term outcome
dc.subject newborn screening
dc.subject severe combined immunodeficiency
dc.subject 22q11.2 deletion syndrome
dc.subject DiGeorge syndrome
dc.subject long-term outcome
dc.subject newborn screening
dc.subject severe combined immunodeficiency
dc.subject T lymphopenia
dc.subject TREC
dc.subject Follow-Up Studies
dc.subject Receptors, Antigen, T-Cell/genetics
dc.subject Humans
dc.subject Neonatal Screening
dc.subject DNA
dc.subject 22q11 Deletion Syndrome
dc.subject Adolescent
dc.subject Lymphopenia/diagnosis
dc.subject Severe Combined Immunodeficiency/diagnosis
dc.subject Infant, Newborn
dc.subject Immunology and Allergy
dc.subject Immunology
dc.title Long-Term Follow-Up of Newborns with 22q11 Deletion Syndrome and Low TRECs
dc.type /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article
dc.description.version Peer reviewed
dc.identifier.pmid 35080750
dc.identifier.doi https://doi.org/10.1007/s10875-021-01201-5
dc.relation.url http://www.scopus.com/inward/record.url?scp=85123620385&partnerID=8YFLogxK
dc.relation.url https://link.springer.com/article/10.1007/s10875-021-01201-5
dc.contributor.department Women's and Childrens's Services

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