- Case-co-twin Studies As a Methodology to Examine the Adversity Immunophenotype While Excluding Genetic Effects: the ImmunoTwin Cohort

Early life adversity (ELA) including social, economic or psychologic factors are known to be decisive drivers of health inequalities in adults. These health inequalities are underpinned by immune, endocrine and epigenetic changes that reflect the interaction with the environment, often reflecting gene-environment interactions. It has not been possible, so far to exclude genetic effects. As monozygotic twins share the same genetic background and perinatal environment, they provide a robust approach to identify the influence of the environment on biological features. The German “TwinLife” cohort has followed over 2,000 twin pairs since 2014 to assess genetic predisposition and environmental influence on health and social outcomes. We screened this cohort for divergence in adverse experience during childhood. We identified over 100 adversity-divergent pairs of monozygotic twins. Here we present how adversity was operationalised and adversity-divergence was measured. Now adversity-divergent twins have been identified, biosampling and psychological profiling is underway to investigate adversity- induced differences in our twin pairs. As immunosenescence and immuneageing are among the more robust biological consequences of adversity, we are performing unbiased mass cytometry profiling. Recently we have shown that Natural Killer cells are functionally degraded after ELA. It remains elusive whether is mediated by epigenetic or other complex molecular mechanisms following exposure to ELA. We are currently examining NK cell maturation state, degranulation capacity, cytotoxicity and DNA methylation status (EPICSv2 arrays) in our adversity-divergent twins. ImmunoTwin is a starting point to highlight the underlying mechanisms of social health inequalities and will allow to provide tomorrow’s prevention tools.