Abstract
BACKGROUND: The antibody repertoire in an infant/toddler develops in response to the microbiome, infections, environmental exposures, and vaccinations. Monitoring the specificity of these antibody responses in normal toddlers will provide indicators of disease susceptibility. METHODS: The serum Immunoglobulin (Ig)G and IgM antibody reactivity patterns in 1- and 2-year-old healthy toddlers was determined by examining the Ig specificity to diverse infectious agents, autoantigens and vaccine antigens with an antigen array. The toddlers were stratified based on their antibody reactivity to these diverse antigens with a normalized fluorescence intensity measure. Repeat profiling was performed at year 2 to reveal longitudinal changes in the IgG and IgM responses. Clinical information, along with DNA sequencing, and selected cytokine assays were used to establish an odds ratio for immune disease potential among the cohort. RESULTS: Healthy 1- and 2- year old IgG responses revealed cohorts of low, moderate, and high Ig responder groups that was unconnected with total serum IgG levels. The high responder group had elevated IgG reactions to selected pathogens, particularly viruses as well as to autoantigens. This high reactivity group, representing 17% of the cohort, had high odds ratios with maternal gestational diabetes, age, and a family history of asthma. While all toddlers developed strong antibody responses to Measles-Mumps-Rubella vaccines (MMR), more variation was noted towards other vaccines. In infections to Molluscum contagiosum, the IgG serum levels were transient regardless of the responder group. The high responder group had DNA polymorphisms linked to enhanced immune responses that correlated with elevated cytokine levels as well as eczema and asthma. A subset of toddlers has strong IgG responses to pathogens and vaccines CONCLUSION: A subset of normal healthy toddlers has a high potential for immune system abnormalities and autoimmunity based on higher serum antibody responses to pathogens and autoantigens, genetic polymorphisms, and elevated cytokine responses. DISCLOSURES: All Authors: No reported disclosures