Objectives: The identification of accurate molecular predictors at presentation of a first demyelinating event (FDE) would complement MRI in assessing risk of subsequent disease course and identifying patients likely to benefit from aggressive treatment. It may indicate cellular activation at FDE.
Methods: We conducted a genome-wide gene expression profiling (GEP) study of CD3+ cells from 11 patients at FDE and 3 months later compared to matched healthy controls. Patients were stratified into 2 groups (inactive and active) based upon clinical and neuroimaging activity at the 3 month time-point. Gene set testing was then used to examine the expression signatures of T-cell subtypes in these groups.
Results: Analysis revealed little difference in the GEP of patients between the two-time points, suggesting a durable expression signal in the first three months following disease onset, irrespective of ongoing disease activity. A regulatory T-cell (Treg) signature gene set was enhanced in both groups at the time of FDE. However, only the inactive group exhibited enhanced signature for FOXP3 regulated gene set, whereas a gene set signature for cytotoxic T-cell activity was only identifiable in the active group.
Conclusions: Using gene set testing we identified correlations between expression signatures of specific cell types and the likelihood of ongoing disease activity. Our findings suggest that peripheral activation of Tregs involving FOXP3 differs between patients with poor or good outcomes. These findings indicate that gene sets characterising the expression signatures of circulating T-cells may be capable of predicting disease course in patients presenting with FDE.