Phenotype of apoptotic lymphocytes in children with Down syndrome

Abstract

Background: Down syndrome (DS) is the most common and best-known chromosomal disorder and is associated with several other pathologic conditions including immunodeficiency which makes a significant contribution to morbidity and mortality. Various immunological theories and observations to explain the predisposition of individuals with DS to various infections have been published, one of which is increased apoptotic cells.

Aim: The aim of this study was to identify the effect of apoptosis on both types of cells of specific immune response (T and B lymphocytes) in children with DS using Annexin V staining of phosphatidyserine (PS) as a specific marker of early apoptosis.

Subjects and methods: The study included 17 children with karyotypically ascertained DS (7 males and 10 females). Their ages ranged from 4 months to 14 years with mean age of 5.7 +/- 4.35 years. Seventeen age and sex matched healthy children were included in the study as controls. Patients or controls with infections were excluded from the study. Complete blood picture, immunophenotyping, analysis of apoptosis using Annexin V was done at National cancer Institute to all children included in this study.

Results: Although CBC, differential count, relative and absolute number of CD(3+) and CD(16+) did not show significant differences between DS children and control group, the relative and the absolute size of apoptotic CD(3+) T lymphocytes, and the relative size of apoptotic CD(19+) B lymphocytes were significantly higher in DS children than in controls. On the other hand, no significant difference was detected as regards the absolute size of CD(19+) B lymphocytes in DS children and in controls

Conclusion: our finding of increased early apoptotic cells (especially T cells) in DS children may emphasize the fact that the function of cells- and not their number- is main mechanism responsible for the impairment of the immune system in DS children and may further add to the known fact that cellular immunity is more severely affected than humoral immunity in these children. Further studies on apoptotic cellular phenotype in larger number of DS are needed.

Figure 1

Flow cytometric analysis of apoptotic CD³⁺ T-lymphocytes in a healthy control. From left to right: 1-dot plot showing gating on total lymphocytes, 2-dot plot showing gating on CD³⁺ T-lymphocytes, 3-dot plot showing the proportion of early apoptotic cells in the upper left quadrant.

Figure 2

Flow cytometric analysis of apoptotic CD³⁺ positive T-lymphocytes in a child with Down syndrome. The percentage of FITC+/PI-in the upper left quadrant (early apoptotic cells), and the FITC+/PI+ in the upper right quadrant (late apoptotic cells) as well as the FITC-/PI+ (necrotic) cells in the lower right quadrant after gating on CD³⁺ cells in a DS child.