High risk blood myeloid dysregulation is elevated in obesity and is reduced by lifestyle interventions 2251787

Abstract Introduction We recently described the Human Immune Dysregulation Evaluation Framework (Hi-DEF) to quantify myeloid and lymphoid dysregulation across infectious and non-infectious illness using peripheral blood gene expression (Moore et al, Nature Medicine). Using the Hi-DEF framework, we evaluated the baseline immune dysregulation in patients with obesity and quantified the changes in immune dysregulation due to lifestyle changes and medical interventions. Methods 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 correlation. 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). Conclusion Patients with obesity have significantly higher myeloid dysregulation compared to healthy subjects, which is modifiable with lifestyle and medical interventions. Funding Source 5K12TR004930-02 Topic Categories Computational and Systems Immunology (COMP)