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

Autor: Framme JL; Department of Pediatrics, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. jenny.lingman-framme@gu.se.; Department of Pediatrics, Halland Hospital Halmstad, Halmstad, Region Halland, Sweden. jenny.lingman-framme@gu.se., Lundqvist C; Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., Lundell AC; Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., van Schouwenburg PA; Department of Pediatrics, Laboratory for Pediatric Immunology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands., Lemarquis AL; Department of Pediatrics, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., Thörn K; Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., Lindgren S; Department of Pediatrics, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.; Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., Gudmundsdottir J; Department of Pediatrics, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.; Children's Medical Center, National University Hospital of Iceland, Reykjavík, Iceland., Lundberg V; Department of Pediatrics, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.; Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., Degerman S; Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.; Department of Clinical Microbiology, Umeå University, Umeå, Sweden., Zetterström RH; Centre for Inherited Metabolic Diseases, Karolinska University Hospital Solna, Stockholm, Sweden.; Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden., Borte S; ImmunoDeficiencyCenter Leipzig (IDCL), Municipal Hospital St. Georg Leipzig, Leipzig, Germany., Hammarström L; Department of Biosciences and Nutrition, Neo, Karolinska Institute, Stockholm, Sweden., Telemo E; Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., Hultdin M; Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden., van der Burg M; Department of Pediatrics, Laboratory for Pediatric Immunology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands., Fasth A; Department of Pediatrics, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., Oskarsdóttir S; Department of Pediatrics, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., Ekwall O; Department of Pediatrics, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.; Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Jazyk: angličtina
Zdroj: Journal of clinical immunology [J Clin Immunol] 2022 Apr; Vol. 42 (3), pp. 618-633. Date of Electronic Publication: 2022 Jan 26.
DOI: 10.1007/s10875-021-01201-5
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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