367 High-risk peripheral blood immune dysregulation signature is elevated in obesity and is reduced by lifestyle interventions

Objectives/Goals: The Human Immune Dysregulation Evaluation Framework (Hi-DEF) quantifies myeloid dysregulation in infectious and non-infectious illness using peripheral blood gene expression (Moore, Nat Med). We evaluated immune dysregulation in obesity and quantified the changes in dysregulation due to lifestyle and medical interventions. Methods/Study Population: We assessed the association of obesity with myeloid dysregulation in the Framingham Cohort using linear regression. In two additional datasets (GSE66175, GSE19790), we assessed the effect of dietary interventions and bariatric surgery on myeloid dysregulation using paired Wilcoxon rank sum test pre- and post- intervention and Pearson’s correlation. Results/Anticipated Results: In the Framingham cohort (n=5321), myeloid dysregulation score was associated with BMI (p=2.2e-6) after correcting for age and sex. Patients assigned to diet/exercise experienced significant reductions in myeloid score after 3 months (n=63, p=1.2e-7), which was not seen in controls (n=63, p=0.29). Change in myeloid score was significantly correlated with change in weight loss (r=0.32, p=0.006). This reduction in myeloid dysregulation was also seen post-bariatric surgery (n=11, p=0.0001). Discussion/Significance of Impact: Patients with obesity have significantly higher myeloid dysregulation compared to healthy subjects, which is modifiable with lifestyle and medical interventions. These results suggest that we may be able to quantify and monitor immune dysregulation from obesity which may place these patients at risk for worse outcomes.