Immune evaluation and vaccine responses in Down syndrome: evidence of immunodeficiency?

Background: Patients with Down syndrome (DS) appear to be at a greater risk for serious infections, but it is unclear whether this is due to anatomic variations or intrinsic immune defects.

Objective: We assessed a cohort of pediatric subjects with DS to determine if immunological abnormalities indeed account for the excess infections.

Methods: We performed quantitative assessment of T-independent (type 2 - pneumococcal polysaccharide vaccine) and T-dependent Ab responses (with inactivated seasonal influenza vaccine) along with numerical quantitation of lymphocyte subpopulations and thymic output in a random population sample of children with DS (cases) along with family-matched sibling or community controls.

Results: Median serum IgG levels were significantly higher in cases (1090 mg/dL) as compared with controls (808 mg/dL, P=0.02). Cases had significantly lower median CD4 T cell counts than the controls (636 cells/μL, P=0.01). Cases had reduced CD19 B cell counts and CD19% than the controls (P=0.009 and 0.006 respectively). Cases also showed decreased total memory (CD19+CD27+, P=0.002) and class-switched memory (CD19+CD27+IgM-IgD-, P=0.004) B cells. The median CD4 recent thymic emigrant (RTE) in females and males cases was lower than controls (P=0.007 and 0.07 respectively). Cases had a lower median T cell receptor excision circle (TREC) count of 2556 as compared to the controls count of 5216, P<0.006 although both the cases and controls were within the established reference range. There were no differences in the percentage of cases and controls who responded to inactivated influenza vaccine, but the response to polysaccharide pneumococcal vaccine was suboptimal in cases.

Conclusions: Our study suggests that there are subtle abnormalities in both humoral and cellular arms of the immune response in children with DS as compared to the control subjects.