Journal
JOURNAL OF CLINICAL IMMUNOLOGY
Volume 42, Issue 3, Pages 618-633Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10875-021-01201-5
Keywords
TREC; newborn screening; 22q11; 2 deletion syndrome; DiGeorge syndrome; severe combined immunodeficiency; T lymphopenia; long-term outcome
Categories
Funding
- University of Gothenburg
- Regional research grant
- Region Halland
- Swedish Research Council [2018-02752]
- Queen Silvia Jubilee Foundation
- Swedish Primary Immunodeficiency Organization
- Sparbanken Foundation
- Varberg
- Frimurare Barnhusdirektionen Foundation
- Gothenburg Medical Society
- Medical Faculty at Umea University
- Cancer Research Foundation in Northern Sweden [AMP 20-1000]
- Swedish government
- county councils, the ALF-agreement [ALFGBG-717431, 718021]
- Umea University [RV-932787, RV-939741]
- Vasterbottens County Council [RV-932787, RV-939741]
- Vinnova [2018-02752] Funding Source: Vinnova
- Swedish Research Council [2018-02752] Funding Source: Swedish Research Council
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This long-term follow-up study reveals that individuals with 22q11DS and low TRECs have persistent immunologic abnormalities and increased risk for immune dysregulation, indicating the necessity of lifelong monitoring.
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 naive T-helper cells, naive T-regulatory cells, naive cytotoxic T cells, and persistently lower TRECs compared to healthy controls. Receptor repertoires showed skewed V-gene usage for naive T-helper cells, whereas for naive 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 naive 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.
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