Genetics

This post covers Kavaka and colleagues' study of monozygotic twins discordant for multiple sclerosis, in which 193,771 CD8 T cells were sequenced from 12 twin pairs split into healthy cotwins, cotwins with subclinical neuroinflammation, and twins with MS. It covers the negative result that cluster proportions do not differ by disease status, the TCR matching that restricts analysis to clones present in both blood and cerebrospinal fluid, the stage-wise gradient in immunological and metabolic signatures with IL2RB marking the subclinical stage, the oxidative phosphorylation finding and what it means therapeutically, the within-pair comparison that controls for genetics, and the cross-sectional limit that keeps the gradient from being a trajectory.