Distinct Abnormalities in the Innate Immune System of Children with Down Syndrome

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^dimCD16⁺ monocytes (147 × 10⁶/L vs 93 × 10⁶/L; P = .02). This difference is fully explained by a higher percentage of CD14^dimCD16⁺ 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 × 10⁶/L vs 22.7 × 10⁶/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 × 10⁶/L vs 3.7 × 10⁶/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^dimCD16⁺ monocytes. This elevated level of CD14^dimCD16⁺ monocytes may play an important role in the onset and maintenance of chronic inflammatory disease in DS.