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Beatrijs Bloemers

Thursday 9 September 2010

Severe RSV infections in children with Down syndrome: the contribution of an impaired immune system

Promotor: Prof.dr J.L.L. Kimpen
Defence: 9 September 2010
Full text

Down syndrome (DS) is the most common chromosomal abnormality among live-born infants. Respiratory tract infections are the most important cause of mortality in individuals with DS at all ages. In this thesis we have described DS to be a risk factor for severe RSV infections. Subsequently, we have shown that children with DS suffer from a high incidence of recurrent wheeze. The relevance of this study is that RSV prevention might be possible using immunoprophylaxis. In recent decades several studies have been performed to elucidate abnormalities of the immune system in DS. In order to clarify the clinical problems frequently seen in this specific population we studied the innate immune system and T-cell dynamics. We showed that insufficient thymic output causes low number of naïve T-cells in children with DS, while peripheral mechanisms regulating the size of the naïve T-cell pool appear intact. In addition, we have shown distinct abnormalities of cells of the innate immune system in children with DS. We have concluded that these immunologic abnormalities might result in decreased viral clearance and thus in the high incidence of respiratory morbidity seen in this specific population.