Autoimmune neurologic diseases
Secondary progressive multiple sclerosis (SPMS) is a chronic neuroimmflammatory disease that develops in many patients following relapsing/remitting multiple sclerosis (RRMS). Whilst RRMS is recognized as an autoimmune disease of the central nervous system, the mechanisms that drive SPMS are yet to be established, but growing evidences indicate immune components also play an important role in SPMS pathogenesis.
We previously reported that the cytotoxic-like CD4+ T cells expressing the transcription factor Eomes (Eomes+ Th cells) are increased in the blood and in cerebrospinal fluid of patients with SPMS, but not RRMS (Raveney et al. Nat. Commun. 2015).
Using a novel mouse model for SPMS, in addition to patient samples, we have carried out further analysis of Eomes+ Th cells to reveal their functional mechanism in chronic autoimmune disease. Importantly, using flow cytometry on post-mortem tissue samples, we have observed for the first time a very high proportion of Eomes+ Th cells amongst brain-infiltrating Th cells only in SPMS, strongly linking these unusual cells with pathogenic processes in this disease.
Furthermore, longitudinal studies confirm our preliminary findings showing an association between Eomes+ Th cell level in blood and current disease activity. High levels of Eomes+ Th cells predicted worsening of disease symptoms as measured by subsequent EDSS changes (positive predictive value, PPV=0.793; negative predictive value, NPV=0.778; FDR=0.179).As SPMS diagnosis currently lacks effective biomarkers, our studies into Eomes+ Th cells and their functional phenotype may provide much-needed prognostic monitoring SPMS activity as well as new therapeutic targets for SPMS treatment.