Serum Antibody Profiling Healthy Toddlers Reveals Low, Intermediate and High Response Cohorts

Abstract

Abstract During their first two years of life, infant/toddlers produce their own antibodies in response to diverse environmental exposures, infections, and vaccinations. The specificity of these antibodies towards self-antigens, infections, and vaccine components and how they vary among individuals is poorly characterized. We developed a new antigen array comprising autoantigens, infectious agents, and vaccine antigens to assess the serum antibody specificities among a cohort of >150 health toddlers. An analysis of their responses reveals a stratification of healthy toddlers into 3 groups, low, intermediate, and high responders. Among those 16% that are high responders, their serum IgGs were able to bind a diverse array of self-antigens as well as infectious agents. Longitudinal follow-up suggests this pattern is relatively stable over time. Comparing clinical data reveals a significant correlation with the high IgG responder cohort and a family history of asthma and maternal gestational diabetes. Targeted DNA sequencing in the high responder group revealed a strong genetic association signal at the HLA locus, with polymorphisms at this locus associated with high ANA and IgG titers to many antigens. Findings from this study may provide insights into the natural history of human autoantibody formation.