Assessment of immune function in Down syndrome patients

In Down syndrome (DS), trisomy 21 leads to overexpression of gene coding for specific enzymes. This overexpression translates directly into biochemical aberrations that affect multiple interacting metabolic pathways which culminates in cellular dysfunction and contributes to the unique pathogenesis of DS. The aim of this study is to evaluate parameters of immune response in terms of cytokines [tumor necrosis factor-α (TNF-α) and interlukin-2 (IL-2)] together with the quantitative expression of cystathionine beta synthase (CBS), whose transsulfuration pathway generates cysteine and hydrogen sulfide (H2S). H2S is known to boost host defense at physiological concentrations and to display cytotoxic activity at higher concentrations. Calcineurin activity (CAN) was also measured as its dysregulation has been shown to cause immune suppression. Subjects were 60 DS patients vs. 30 age and socioeconomic matching healthy controls. In their blood, the cytokines: TNF-α and IL-2, together with CBS and its by product H2S as well as CAN activity, were measured. Results showed that CBSmRNA relative expression (0.56 ± .06 vs. 0.32 ± .02), plasma H2S (72 ± 8.5 vs. 50.8 ± 4.1) and TNF-α (8.11 ± .01 vs. 3.6 ± 0.9) were significantly higher among DS patients compared to controls, while CAN (0.27 ± 0.1 vs. 0.45 ± 0.2 units), was significantly decreased in blood of DS patients compared to controls. IL-2 (36.4 ± 2.6 vs. 37.4 ± 0.9) showed no significant difference between DS patients and controls. Accordingly it can be concluded that excessive synthesis of multiple gene products derived from overexpression of the genes present on chromosome 21 may be the cause for decreased immunity in DS patients compared to controls.