Deep immune phenotyping reveals similarities between aging, Down syndrome, and autoimmunity
Katharina Lambert, Keagan G. Moo, Azlann Arnett, Gautam Goel, Alex Hu, Kaitlin J. Flynn, Cate Speake, Alice E. Wiedeman, Vivian H. Gersuk, Peter S. Linsley, Carla J. Greenbaum, S. Alice Long, Rebecca Partridge, Jane H. Buckner, Bernard Khor
Abstract
T cells in individuals with Down syndrome and identified interleukin-6 as a candidate driver of some of these changes, thus extending the consideration of immunopathologic cytokines in Down syndrome beyond interferons. We used immune cellular composition to generate three linear models of aging (immune clocks) trained on control participants. All three immune clocks demonstrated advanced immune aging in individuals with Down syndrome. One of these clocks, informed by Down syndrome–relevant biology, also showed advanced immune aging in individuals with type 1 diabetes. Orthologous RNA sequencing–derived immune clocks also demonstrated advanced immune aging in individuals with Down syndrome. Together, our findings demonstrate an approach to studying immune aging in Down syndrome that may have implications in other autoimmune diseases.