Background: Trisomy 21 is associated with an increased susceptibility to respiratory infections.
Objective and hypotheses: For a more detailed characterization of the adaptive immune response, we analyzed the cellular and humoral immunity to specific pathogens in blood samples of 40 children with Downs syndrome in comparison to 51 age-matched controls.
Method: We quantitatively analyzed lymphocyte subpopulations using flow cytometry. In addition, the T-cell effector function was characterized by functional and phenotypical analysis after polyclonal stimulation with staphylococcal enterotoxin (SEB) and antigen-specific stimulation with antigens of Varicella zoster virus (VZV), Cytomegalovirus (CMV) and M.tuberculosis (tuberculin). Results were correlated with humoral immune responses.
Results: The proportion of NK-cells within the lymphocytes of children with Downs syndrome was strikingly increased whereas the B-cell percentage was decreased. While the total amount of T-cells showed no differences, children with Downs syndrome revealed less CD4+ and more CD4+CD8+T-cells. Within the CD4+T-cell population, we detected a higher percentage of regulatory and Th17-cells and a higher Th1/Th2 ratio as well as a higher expression of the anergy markers PD-1 and CTLA-4. Percentages of polyclonally activated cells were significantly higher in children with Downs syndrome and showed an altered expression profile of the cytokines INFγ, TNFα and IL-2. Analysis of pathogen-specific immune responses showed an age-appropriate level of endemic infection with CMV, VZV and mycobacteria in both groups. CMV-specific cellular and humoral immunity correlated in all children. Among VZV IgG positive children, a higher percentage of VZV-specific T-cell-positive individuals were seen in the Downs syndrome group.
Conclusion: No pronounced differences were detectable in pathogen-specific immune responses of children with Downs syndrome and controls. Besides a general proportional shift of leukocyte and lymphocyte subpopulations, effector T-cells seem to be functionally impaired which may promote a higher susceptibility to infections. The simultaneously higher fraction of reactive effector T-cells could represent a compensatory effect of functional anergy and/or be a consequence of a more pronounced history of infection.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology