A prospective study of influenza vaccination and a comparison of immunologic parameters in children and adults with chromosome 22q11.2 deletion syndrome (digeorge syndrome/velocardiofacial syndrome)

Abstract

Prior to the advent of cardiac bypass, most children with congenital cardiac anomalies and chromosome 22q11.2 deletion syndrome died. With improved technology, there is now a wave of young adults with chromosome 22q11.2 deletion syndrome requiring clinical care. Fifteen young children and 20 adults with chromosome 22q11.2 deletion had flow cytometry, functional T cell analyses, and functional B cell analyses to characterize their immune system. Subjects were vaccinated with the annual inactivated influenza vaccine, and responses were evaluated by hemagglutination inhibition titer assessment. The pattern of T cell subset abnormalities was markedly different between pediatric and adult patients. In spite of the cellular deficits observed in adults, titers produced after influenza vaccine administration were largely intact. We conclude that disruption to T cell production appears to have secondary consequences for T cell differentiation and B cell function although the clinical impact remains to be determined.

Fig. 1

T cell subsets. Functionally distinct T cell subsets were enumerated by flow cytometry. Patients and controls were compared. The graphs display means ± standard deviations and asterisks indicate statistical significance. The p values are given in the text. T cell counts were globally higher in children than in adults and the y-axes are different between the two age groups. Comparing pediatric patients and controls, the most significant differences were the diminished naive, central memory, and regulatory subsets in the CD4 compartment and the diminished naive and central memory subsets in the CD8 compartment. In adult patients, it was the CD4 effector and reverted memory subsets that were diminished

Fig. 2

B cell subsets. Distinct B cell subsets were enumerated by flow cytometry. Patients and controls were compared. The top panels display stacked bar graphs summarizing the composition of the B cell compartment in each cohort. The stacked bar graphs compare the contribution of each subset to the total. The left panel displays the composition as a fraction of the total B cell compartment while the right panel displays the absolute counts of each subset. The only statistically significant differences are the CD5 (B1 B cells) and the switched memory B cells in adults, although the overall composition of the B cell compartment appears disordered in both sets of patients. In the children, the less mature subsets are contracted, while in the adults, it is the more mature subsets that are contracted. In the bottom panel, B cell function was assessed. Total IgG responses were measured by B cell ELISPOT using anti-IgG as the stimulus. Adult patients had compromised immunoglobulin production compared to adult controls

Fig. 3

Vaccine responses. We defined the responder frequency as the percent of subjects who developed a fourfold increase in titer to any serotype. There were no statistically significant differences in responder frequency between the groups. All populations exhibited an increase in geometric mean titer after vaccination. The B cell ELISPOT analysis demonstrated that only the adult controls had a significant rise after vaccination. The graphs display means ± standard deviations. Asterisks are used to indicate statistical significance