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- Gudmundsdottir, J. A., et al.
(författare)
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Normal neonatal TREC and KREC levels in early onset juvenile idiopathic arthritis
- 2023
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Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616 .- 1521-7035. ; 249
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Dysregulated central tolerance predisposes to autoimmune diseases. Reduced thymic output as well as compromised central B cell tolerance checkpoints have been proposed in the pathogenesis of juvenile idiopathic arthritis (JIA). The aim of this study was to investigate neonatal levels of T-cell receptor excision circles (TRECs) and kappa-deleting element excision circles (KRECs), as markers of T-and B-cell output at birth, in patients with early onset JIA.Methods: TRECs and KRECs were quantitated by multiplex qPCR from dried blood spots (DBS), collected 2-5 days after birth, in 156 children with early onset JIA and in 312 matched controls.Results: When analysed from neonatal dried blood spots, the median TREC level was 78 (IQR 55-113) in JIA cases and 88 (IQR 57-117) copies/well in controls. The median KREC level was 51 (IQR 35-69) and 53 (IQR 35-74) copies/well, in JIA cases and controls, respectively. Stratification by sex and age at disease onset did not reveal any difference in the levels of TRECs and KRECs.Conclusion: T-and B-cell output at birth, as measured by TREC and KREC levels in neonatal dried blood spots, does not differ in children with early onset JIA compared to controls.
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| 2. |
- Lingman Framme, Jenny, 1977
(författare)
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Thymus dysfunction in the 22q11 deletion syndrome
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The 22q11.2 deletion syndrome (22q11DS) is associated with heterogeneous clinical findings, including T-cell immunodeficiency resulting from thymus hypoplasia. Newborn screening programs based on the quantification of T-cell receptor excision circles (TRECs) identify infants with severe combined immunodeficiency, as well as a number of infants with 22q11DS. Aim: To study the outcome of TRECs at birth in infants with 22q11DS, and to investigate if low numbers of TRECs are predictive of persistent thymus dysfunction in individuals with 22q11DS. Method: TRECs were retrospectively quantified by PCR using the original newborn screening cards from 48 infants with 22q11DS (Paper I). A follow-up of individuals with low numbers of TRECs (22q11Low, N=10), normal numbers of TRECs (22q11Normal, N=10) and matched healthy controls (N=10), was performed, including quantification of TRECs, flow cytometry for characterization of lymphocyte subsets, deep sequencing of T-cell receptor repertoires, and PCR for assessment of telomere lengths (Paper II). High-density arrays were used for autoantibody profiling (Paper III). Results: A considerable proportion of infants with 22q11DS had abnormal numbers of TRECs at birth (Paper I). At follow-up (median age 16 years), the 22q11Low group had lower TRECs, lower proportions of naïve T cells, aberrant T-cell receptor repertoires (Paper II) and more autoantibodies (Paper III), as compared to the 22q11Normal group and to healthy controls. Many autoantibody specificities were shared between the two 22q11DS groups. Conclusion: Newborn screening with TRECs identifies a subpopulation of infants with 22q11DS, in whom low numbers of TRECs at birth are associated with long-term immune aberrations, necessitating follow-up.
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