Abdel-Meguid, I. E., E. Abdel-Salam, D. A. M. Latif, S. Korraa, and A. Ismaiel, "Markers of neural degeneration and regeneration in Down syndrome patients", Egyptian Journal of Medical Human Genetics, vol. 14, issue 1, pp. 49–53, 2013. Abstract

On the trisomy Down syndrome Critical Region (DSCR1) is located the APP gene, which accelerates amyloid peptide protein (APP) expression leading to cerebral accumulation of APP-derived amyloid-beta peptides (Aβ) and age-dependent cognitive sequelae. Also DSCR1 attenuates endothelial cell proliferation and angiogenesis required for tissue repair. The aim of the present work is to determine markers of neural degeneration and regeneration in the blood of young and adolescent Down syndrome (DS) patients as well as controls. Markers of regeneration were measured in terms of circulating mononuclear cells expressing Nestin and CD34, while markers of degeneration were measured in terms of plasma Aβ42 and advanced glycation end products receptors (RAGES). Results showed a significant increase in plasma Aβ42 (20 ± 5.1 vs. 11.9 ± 3.4) and RAGES leucocytes mRNA relative expression (1.9 ± 0.2 vs. 1.1 ± 0.6) in adolescent DS patients compared to young DS. Both parameters were also significantly increased in DS compared to controls: Aβ42 (15.4 ± 5.9 vs. 12. 3 ± 4.5); RAGES (1.4 ± 0.5 vs. 0.7 ± 0.2). Nestin (5.2 ± 1.4 vs. 6.3 ± 0.6) and CD34 (52 ± 2.5 vs. 53 ± 4.7) were non-significantly lower in adolescent DS patients compared to young DS, but significantly lower in DS patients compared to controls: Nestin (6.3 ± 1.5 vs. 9 ± 4.4); CD34 (54 ± 3.4 vs. 60 ± 4.8). The significant decrease in the number of mononuclear cells bearing Nestin and CD34 markers accompanied by a significant increase in Aβ42 and RAGES indicate that degeneration in DS is an ongoing process, which is not counterbalanced by the regenerative mechanism.

Abdel-Salam, E., I. Abdel-Meguid, and S. Korraa, "Assessment of immune function in Down syndrome patients", Egyptian Journal of Medical Human Genetics, vol. 14, issue 3, pp. 307–310, 2013. Abstract

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.