The overexpression of genes resulting from trisomy 21 in Down syndrome may be responsible for many of the abnormalities of the immune system reported in Down syndrome. The level of superoxide disimutase-1, which is coded by a gene on chromosome 21, is on average, 150% of the values found in normal individuals’ blood as well as other cells. The high enzyme activity results in a high rate of conversion of superoxides to peroxides, resulting in high levels of peroxides that may damage DNA and lipids, and in low levels of the superoxides that are essential for killing microorganisms such as Staphylococcus aureus and Candida albicans.

Over expression of lymphocyte function associated antigen-1(LFA-1), which is also coded on chromosome 21, may lead to an abnormal interaction between cells from the thymus, resulting in aberrant T-cell maturation and selection. Overexpression of the interferon receptor gene also located on chromosome 21 is common in Down syndrome and may also contribute to immune deficiency. Low serum zinc common in Down syndrome, may also cause weak immunity.

The most significant abnormality of the immune system in Down syndrome is a 30-fold increase in the incidence of acute leukemia and a 200-fold increase in acute megakaryocytic leukemia. 30% of adults with Down syndrome are deficient in IgG-2 and/or IgG-4 and these deficiencies are also common in children with Down syndrome. Elevations of IgG-1 and IgG-3 are common in persons with Down syndrome. In children with the abnormal immunoglobulin pattern, selenium supplementation at a dose of 10 mcg/kg (4.54 mcg/lb.) body weight for six months significantly increased IgG-2 and IgG-4 levels and reduced the number of infections.

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