Immune Signatures of Prodromal Multiple Sclerosis in Monozygotic Twins
30 Pages Posted: 5 Sep 2019 Sneak Peek Status: Review CompleteMore...
The tremendous heterogeneity of the human population presents a major obstacle in understanding how autoimmune diseases like Multiple Sclerosis (MS) contribute to variations in human peripheral immune signatures. To minimize heterogeneity, we investigated a unique cohort of monozygotic twin pairs who were clinically discordant for MS. Notably, a subgroup of the clinically healthy twins exhibited signs of subclinical, prodromal MS. Comprehensive immune phenotyping revealed that in the overall cohort, the immune signatures of MS-affected and unaffected co-twins were remarkably similar. Twinship alone contributed 68% of the immune variation, whereas age, sex and MS together only contributed 8%. However, distinct traits in CD4+ and CD8+ effector T cell populations emerged when we focused on the subgroup with prodromal MS. These early-disease immune traits were confirmed in a second independent cohort of untreated early relapsing-remitting MS patients. Early involvement of effector T cell subsets points to a key role of T cells in MS disease initiation.
Keywords: monozygotic twin study, prodromal multiple sclerosis, deep immune phenotyping
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