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Down Syndrome Abstract
of the Month: Sept 2001

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Immune-endocrine status and coeliac disease in children with Down's syndrome: relationships with zinc and cognitive efficiency.

Licastro F, Mariani RA, Faldella G, Carpene E, Guidicini G, Rangoni A, Grilli T, Bazzocchi G
Brain Res Bull 2001 May 15;55(2):313-317

Department of Experimental Pathology, University of Bologna, Bologna, Italy

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Immune defects, thyroid abnormalities, plasma zinc levels, and the presence of gastrointestinal disease were investigated in 43 children with Down's syndrome (DS). Peripheral T lymphocytes with the phenotype of helper cells or cluster of differentiation 4 (CD4) were decreased. Circulating activated T cells (CD3/HLA-DR-positive cells) and large granular lymphocytes (CD16/CD56 positive cells) were increased. Plasma levels of interleukin-6 were higher in DS children than in controls. Serum levels of thyroid-stimulating hormone were increased in DS. Coeliac disease was over-represented in the group of DS children and many of these children also showed increased serum levels of immunoglobulin-G (IgG) specific for gliadin antigen. The increment of serum interleukin-6 was age-related and correlated with anti-gliadin IgG levels in DS. Plasma zinc levels were lower in DS children with coeliac disease and in those with anti-gliadin IgG than in DS without detectable anti-gliadin IgG. Dietary antigens may represent a continuous stimulus for the immune system in this syndrome and interfere with normal immune responses. Altered intestinal absorption of nutrients may in turn affect endocrine functions, brain development, and cognitive performances.

My comments:

The title of this paper is confusing: the authors are not comparing zinc to cognitive skill, but the effects of celiac disease on the immune system, and the effect of these changes on cognition. Cognition was defined by results of a comprehension test, which were not detailed in the study. Out of 43 children with DS studied, 4 had evidence of celiac disease; this number was too small to make adequate comparisons between the immune status of these children and the other children with DS without celiac disease.

The abnormalities of the immune system of children with DS presented here have been recounted in other studies as well. An immature thymus gland in children with DS appears to prevent the T-cells from developing correctly, thus leading to a decreased antibody response to certain infections.

Interleukin-6 is a protein that has been suggested to be somehow associated with Alzheimer's disease; one study showed a correlation between high levels of this protein and the severity of dementia in adults with DS and Alzheimer's. However, the present study found no statistical significance between the levels of this protein and cognitive performance in children with DS.

I was disappointed to see the authors use IgG anti-gliadin levels instead of the more appropriate IgA anti-gliadin. Increased IgG anti-gliadin does not correlate well with celiac disease, but rather with intestinal exposure to gliadin. I'm not convinced the authors proved their supposition. The last sentence of the above abstract is pure speculation and not borne out by any of the data in this study. Overall, not a satisfying article.

The authors close their report by stating that they are in the process of studying the effects of selected vitamins and micronutrients on the immune system of children with DS.

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