A pilot study of immunorespons in children with Down syndrome after Respiratory Syncytial Virus (RSV) lower respiratory tract infections (LRTI)

Respiratory syncytial virus (RSV) is the single most important cause of lower
respiratory tract infections (LRTI) in infants and young children. Seventy
percent of infants will be infected with RSV before one year of age, and
virtually all children have had a RSV LRTI before the age of 2 years. Most
children will develop a minor cold, but in 22% of cases children develop severe
RSV bronchiolitis. About 3% of all children are hospitalized, 7-22% of which is
in need of mechanical ventilation.
Down syndrome (DS) is the most common chromosomal abnormality among live born
infants. DS is associated with a variety of immunological impairments. Lower
respiratory tract infection is the most common cause for acute hospital
admission in children with DS. In a recent study (article in preparation) we
found an increased incidence of RSV LRTI hospitalization in children with DS.
The factors that determine the high risk of RSV LRTI hospitalization in
children with DS are currently unclear. Different pathophysiologic mechanisms
could play a role. For instance, children with DS appear to have suboptimal
immune responses. Thymus development and function is abnormal. The number of
B-cells and T-cells are low, especially in the first two years of life. In
addition, defective T-cell ex vivo proliferative responses to non-specific and
antigenic stimuli, cytokine production and NK-cell responses are thought to
play a role in the increased susceptibility to infectious pathogens. Our
hypothesis is that an abnormal innate and acquired immunorespons predisposes
children with DS for severe RSV LRTI.

The primary objective is whether a difference in innate and acquired
immunorespons on RSV infection exists, in children with DS compared to healthy
matched-controls.

This is an observational study. In a total of 100 children (50 DS and 50
healthy matched-controls) innate and acquired immunorespons against RSV will be
examined. A single venapunction will be done, to acquire 5-10 ml blood (if
possible this will be done in combination with a planned diagnostic
venapunction).
Part of this blood will be cultured in the presence of live RSV. Cytokine
respons will be measured after 5 days. Further, FACS staining will be done to
measure the amount of virus specific cells. Stimulation assays will be
performed to examine specific T-cell responses. Finally, part of the blood will
be used to determine the amount and function of dendritic cells after RSV
infection. In case of rest-material and if parental consent has been given,
this will be frozen for possible future studies, for which parental consent
will be asked again at that time.

All participants will undergo one venapunction during a regular visit to the
outpatient clinic or during an elective procedure. Patients will not come to
the hospital particularly for this study, unless this is not possible
otherwise. The amount of time for a venapunction is limited, usually it does
not take more than 10 minutes. The risks of a venapunction is negligible. The
possibility of a haematoma or prolonged bleeding must be taken into account.
The consequences are limited however. In case of unsuspected serious adverse
events, this will be reported to both parents and the METC. The most important
burden to be taken into account is the venapunction, which can be fearful or
stressing for the child. The parent will be asked to accompany the child during
the venapunction to report signals of a high burden for the child, so that in
consultation with the parent the procedure will be ceased.