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Distinct abnormalities in the innate immune system of children with Down syndrome
Beatrijs L P Bloemers1, Grada M van Bleek, Jan L L Kimpen
1Department of Pediatrics, Division of Infectious Diseases and Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Insights
Children with Down syndrome (DS) show immune system differences, including higher numbers of proinflammatory CD14(dim)CD16(+) monocytes. These immune changes may contribute to chronic inflammation in DS.
Area of Science:
- Immunology
- Genetics
- Pediatrics
Background:
- Down syndrome (DS) is associated with immune dysregulation.
- Understanding innate immune cell profiles in DS is crucial for managing associated health conditions.
Purpose of the Study:
- To investigate the frequency and phenotype of innate immune cells in the peripheral blood of children with Down syndrome.
- To identify specific immune cell abnormalities that may contribute to the pathophysiology of DS.
Main Methods:
- Flow cytometry was used to analyze cell surface markers on peripheral blood cells.
- The study included 41 children with DS and 41 age-matched healthy controls.
Main Results:
- Children with DS had lower total leukocyte, lymphocyte, monocyte, and granulocyte counts.
- A significant increase in CD14(dim)CD16(+) monocytes was observed in children with DS (28.7% vs 13.4%).
- Absolute numbers of myeloid dendritic cells and invariant natural killer T cells were lower in children with DS.
Conclusions:
- Children with DS exhibit distinct innate immune system abnormalities.
- Elevated levels of proinflammatory CD14(dim)CD16(+) monocytes in DS may be linked to chronic inflammation.
- These findings highlight potential targets for therapeutic interventions in DS.
Objective:
To analyze the frequency and phenotype of cells of the innate immune system in the peripheral blood of children with Down syndrome (DS).
Study Design:
Flow cytometric analysis of expression of cell surface markers was performed in children with DS (n = 41) and healthy age-matched controls (n = 41).
Results:
Compared with controls, children with DS had significantly lower absolute total leukocyte counts, lymphocytes, monocytes, and granulocytes, but 1.5-times higher absolute numbers of CD14(dim)CD16(+) monocytes (147 x 10(6)/L vs 93 x 10(6)/L; P = .02). This difference is fully explained by a higher percentage of CD14(dim)CD16(+) monocytes within the monocyte compartment (28.7% vs 13.4%; P <.001). The absolute numbers of myeloid dendritic cells were lower in DS (13.8 x 10(6)/L vs 22.7 x 10(6)/L; P <.001). The numbers of plasmacytoid dendritic cells and natural killer cells were normal. Absolute numbers of invariant natural killer T cells were very low overall, but significantly lower in children with DS than in controls (1.2 x 10(6)/L vs 3.7 x 10(6)/L; P = .01).
Conclusions:
Children with DS exhibited distinct abnormalities in cells of the innate immune system. Most strikingly, they had a high number of proinflammatory CD14(dim)CD16(+) monocytes. This elevated level of CD14(dim)CD16(+) monocytes may play an important role in the onset and maintenance of chronic inflammatory disease in DS.
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