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

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


Title: Long-Term Follow-Up of Newborns with 22q11 Deletion Syndrome and Low TRECs
Author: Framme, Jenny Lingman
Lundqvist, Christina
Lundell, Anna Carin
van Schouwenburg, Pauline A.
Lemarquis, Andri L.
Thörn, Karolina
Lindgren, Susanne
Gudmundsdottir, Judith
Lundberg, Vanja
Degerman, Sofie
... 9 more authors Show all authors
Date: 2022-01
Language: English
Scope:
Department: Women's and Childrens's Services
Series: Journal of Clinical Immunology; ()
ISSN: 0271-9142
DOI: https://doi.org/10.1007/s10875-021-01201-5
Subject: Barnalæknisfræði; 22q11.2 deletion syndrome; DiGeorge syndrome; long-term outcome; newborn screening; severe combined immunodeficiency; T lymphopenia; TREC; Immunology and Allergy; Immunology
URI: https://hdl.handle.net/20.500.11815/3018

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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 . https://doi.org/10.1007/s10875-021-01201-5

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.

Description:

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).

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