172. Serum Igg Profiling Healthy 1- and 2- year Old Toddlers Reveals a Subgroup with Clinically Informative Reactivities to Pathogens and Autoantigens

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

Effect of a Small Selective Inhibitor of C-Jun N-Terminal Kinase on the Inducible mRNA Expression of Interleukin-6 and Interleukin-18

BACKGROUND: The expression of many inducible genes, involved in cell growth and differentiation as cytokine genes are regulated by receptor-activated intracellular signalling pathways, including the c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase pathway. AIM: We examined the involvement of the JNK signalling pathway in the regulation of the inducible interleukin-6 (IL-6) and interleukin-18 (IL-18) gene expression at the transcriptional level. METHODS: Peripheral blood mononuclear cells (PBMC) from healthy donors were stimulated with lipopolysaccharide (LPS) and C3 binding glycoprotein (C3bgp) with or without SP600125 and cultured for 6 h. After mRNA isolation, a qRT-PCR was performed. RESULTS: Regarding IL-6 and IL-18 mRNA expression, donors were divided into two groups of high and low responders. SP600125 inhibited significantly IL-6 mRNA transcription in the high responder group and did not influence the transcription level in the low responder group. Concerning IL-18 mRNA, we detect the significant effect of SP600125 on the inducible mRNA in high responder group upon C3bgp stimulation. CONCLUSION: JNK transduction pathway is involved in the production of IL-6 mRNA, after LPS and C3bgp stimulation. We suggest that the inhibition of JNK may be beneficial only for higher responding patients during the treatment of inflammatory and autoimmune diseases.